Effects of microencapsulated blend of organic acids and botanicals on growth performance, intestinal barrier function, inflammatory cytokines, and endocannabinoid system gene expression in broiler chickens.

With restricted usage of growth-promoting antibiotics, identifying alternative feed additives that both improve intestinal barrier function and reduce inflammation is the center to improve chickens' health. This study examined the effects of a microencapsulated feed additive containing citric acid, sorbic acids, thymol, and vanillin on intestinal barrier function and inflammation status. A total of 240 birds were assigned to either a commercial control diet or control diet supplemented with 500 g/MT of the microencapsulated additive product. Birds were raised by feeding a 2-phase diet (starter, d 1 to d 21; and grower, d 15 to d 42). Growth performance was recorded weekly. At d 21 and d 42, total gastrointestinal tract permeability was evaluated by FITC-dextran (FD4) oral gavage. Jejunum-specific barrier functions were evaluated by Ussing chamber. Intestinal gene expression of selected epithelial cell markers, tight junction (TJ) proteins, inflammatory cytokines, and endocannabinoid system (ECS) markers were determined by RT-PCR. Statistical analysis was performed using Student t test. Results showed significant improvement of feed efficiency in the birds supplemented with the blend of organic acids and botanicals. At d 21, both oral and jejunal FD4 permeability were lower in the supplemented group. Jejunal transepithelial resistance was higher in the supplemented birds. At d 21, expression of TJs mRNA (CLDN1 and ZO2) was both upregulated in the jejunum and ileum of supplemented birds, while CLDN2 was downregulated in cecum. Proliferating cell marker SOX9 was higher expressed in jejunum and ceca. Goblet cell marker (MUC2) was upregulated, while Paneth cell marker (LYZ) was downregulated in the ileum. Proinflammatory cytokine expressions of IL1B, TNFA, and IFNG were downregulated in jejunum, while anti-inflammatory IL10 expression was higher in jejunum, ileum, cecum, and cecal tonsil. The ECS markers expressions were upregulated in most intestinal regions. Together, these results demonstrated that the blend of organic acids and botanical supplementation reduced inflammation, improved the TJs expression and intestinal barrier function, and thus improved chicken feed efficiency. The activated ECS may play a role in reducing intestinal tissue inflammation.

Variable accuracy, precision, and consistency of compounded famciclovir formulated for management of feline herpesvirus-1 in cats.

OBJECTIVE: To evaluate compounded famciclovir suspensions for accuracy, precision, and consistency in drug content. PROCEDURES: Two compounded famciclovir concentrations were evaluated (250 and 400 mg/mL, 30 preparations total from nine 503A compounding pharmacies) with U.S. Food and Drug Administration (FDA)-approved famciclovir tablets as control. Drug quantification via high-performance liquid chromatography (with famciclovir reference standard and pramipexole internal standard) was performed at 0, 14, and 28 days with concentrations of 90%-110% of labeled dose considered acceptable (US Pharmacopoeia standards). RESULTS: FDA-approved tablets from three different manufacturers were found to be accurate and precise with acceptable drug content. A significantly greater mean deviation from labeled content was noted for 400 mg/mL suspensions (-52.9%) compared to 250 mg/mL suspensions (-18.0%). When assessing time points separately, 15/63 (24%) samples of 250 mg/mL and 0/27 (0%) samples of 400 mg/mL suspensions met the acceptance standards. Coefficients of variation (CV) in drug content among pharmacy batches ranged from 0.5% to 29%, with 5/10 formulations having significantly lower CV% compared to control (decreased precision). Similarly, drug content changed over time (0-28 days) in all compounded formulations, with both downward and upward trends observed (variable consistency). CONCLUSIONS: Most compounded famciclovir formulations were inaccurate, imprecise, and inconsistent. FDA-approved famciclovir tablets may be preferred over compounded famciclovir formulations for the management of feline herpesvirus-1. If compounded famciclovir is used in practice, a concentration of 250 mg/mL is preferred over 400 mg/mL given the lower accuracy of the higher concentration.

Therapeutic equivalence of ivermectin 1% and two novel formulations combined of ivermectin 1% + fluazuron 12.5% for the control of Rhipicephalus (Boophilus) microplus in beef cattle from Uruguay.

Background: Novel combinations of ivermectin (IVM) and fluazuron (FLU) are presented as an alternative for the control of ticks in cattle. Applying a combination of drugs with the aim to affect different stages of the parasite's life cycle is established as a potential measure to achieve the control of ticks in cattle. Aim: To determine the therapeutic equivalence between two novel formulations of IVM 1% combined with FLU 12.5% tested on bovines naturally infested with Rhipicephalus (Boophilus) microplus. Methods: Forty adult beef cattle were randomized into four groups (n = 10): IVM [1% (0.2 mg/kg)], combinations groups A and B [IVM 1% (0.2 mg/kg) + FLU 12.5% (2.5 mg/kg), each], and control [untreated]). On days 14, 27, and 49 after administration, the presence of ticks was ranked as null, low, medium, and high; a cumulative link model was adjusted to evaluate treatment response. Results: Although all groups had some animals with the presence of ticks until day 27, on day 14 IVM [odds ratios (OR) 0.013, CI95%: 0.001-0.014, p < 0.01], A (OR 0.01, CI95%: 0.00-0.07, p < 0.01) and B (OR 0.01, CI95%: 0.00-0.148, p < 0.01) groups were different when compared to the control group, unlike on day 27 where only groups A (OR 0.02, CI95%: 0.00-0.17, p < 0.01) and B (OR 0.06, CI95%: 0.00-0.46, p < 0.01) remained different from the control group. On day 49 post-administration, IVM and B did not differ from the control group, with 0.95 probability (CI95% 0.92-1.02) of high parasite burden. At day 49 post-administration, group A was the only group free of ticks (OR 0.01, CI95%: 0.00-0.13, p < 0.01). Conclusions: Pharmacotechnical differences in combined formulations should be considered in therapeutic equivalence studies.

Evaluation of partial area under the curve in bioequivalence studies using destructive sampling design.

Product blood-level in vivo bioequivalence (BE) studies typically involve complete blood concentration-time profiles generated for each subject. Accordingly, each subject provides the estimates of the rate and extent of drug absorption. However, repeated blood draws are not always feasible for studies using small animals because of handling or blood volume (e.g., fish or in toxicokinetic studies when only single samples can be taken per animal). Although several proposals have been published for comparing the product extent of absorption, the issue of comparative absorption rates remains unresolved. In this paper, we propose to apply the Bailer-Satterthwaite-Fieller confidence interval for estimating the ratio of partial area under the curve in studies that use a destructive sampling design (one blood sample per subject). To characterize the behavior of this alternative approach, we examine the impact of partial area cutoff time, blood sampling schedule, and the number of subjects included at each sampling time. Using simulated situations reflective of the issues encountered with immediate-release veterinary formulations, we compare BE conclusions resulting from the use of this approach with simulated results that assuming repeated blood draws from each study subject.

Drug content on receipt and over time for compounded formulations of famciclovir.

OBJECTIVES: The aim of this study was to determine famciclovir content (strength) in compounded formulations and to determine if potency changed over time. METHODS: Four concentrations of oral oil suspension in three distinct flavors, three concentrations of oral paste, three chew treats and 62.5 mg tablets from one compounding pharmacy were evaluated for famciclovir content. Specific sample preparation procedures were used for each drug formulation prior to determination of famciclovir content through mass spectrometry tandem liquid chromatography. Analysis was performed on arrival from the compounder and on days 7, 14, 28, 56 and 120. Samples were run in triplicate and concentration determined by comparison with a standard curve. Content was considered appropriate if within 90-110% of the labeled concentration. RESULTS: On arrival from the compounding pharmacy, 5/12 oral oil suspensions of varying concentrations were <90% of the labeled concentration and 3/3 oral pastes were >110%. Famciclovir content in oil suspensions ranged from 72% to 118% of the label value while oral pastes ranged from 95% to 202% of the label concentration over the 120 study days, and all concentrations varied in an unpredictable fashion. Tablets contained 90-110% of the labeled value throughout the study period. Chew treats could not be successfully analyzed. CONCLUSIONS AND RELEVANCE: This study found substantial variation in famciclovir content in the compounded products evaluated, which, in turn, raises concerns that substandard dosing could result in lack of efficacy or a failed treatment trial. Drug toxicity might also be encountered. Veterinarians must be aware that while compounded medications can improve compliance, they might not deliver the drug dose expected.

Design and in vivo evaluation of a microparticulate depot formulation of buprenorphine for veterinary use.

Buprenorphine is a frequently used analgetic agent in veterinary medicine. A major drawback, however, is the short duration of action requiring several daily administrations. We therefore designed a poly-lactic-co-glycolic acid (PLGA) based microparticulate drug formulation for sustained parenteral drug release. Particles were designed to allow for a fast onset of action and a duration of the analgesic effect of at least two days in laboratory mice. Microparticles were produced using a solvent evaporation technique. Release rate was dependent on polymer type and particle size. Spherical particles used for subsequent animal studies had a mean size of 50 µm and contained 4.5% of buprenorphine. Drug release was characterized by an initial burst release of 30% followed by complete release over seven days. In vivo pharmacokinetic experiments in female C57BL/6 J mice confirmed prolonged exposure in plasma and brain tissue and correlated with the pharmacological effect in the hot plate assay or after minor abdominal surgery. No adverse side effects with respect to food and water intake, body weight, local tolerability, or nesting behavior were observed. Our formulation is an attractive alternative to established immediate release formulations. A use for prolonged pain management in laboratory animals is proposed.

Effects of a microencapsulated formula of organic acids and essential oils on nutrient absorption, immunity, gut barrier function, and abundance of enterotoxigenic Escherichia coli F4 in weaned piglets challenged with E. coli F4.

The objective was to study the effects of microencapsulated organic acids (OA) and essential oils (EO) on growth performance, immune system, gut barrier function, nutrient digestion and absorption, and abundance of enterotoxigenic Escherichia coli F4 (ETEC F4) in the weaned piglets challenged with ETEC F4. Twenty-four ETEC F4 susceptible weaned piglets were randomly distributed to 4 treatments including (1) sham-challenged control (SSC; piglets fed a control diet and challenged with phosphate-buffered saline (PBS)); (2) challenged control (CC; piglets fed a control diet and challenged with ETEC F4); (3) antibiotic growth promoters (AGP; CC + 55 mg·kg-1 of Aureomycin); and (4) microencapsulated OA and EO [P(OA+EO); (CC + 2 g·kg-1 of microencapsulated OA and EO]. The ETEC F4 infection significantly induced diarrhea at 8, 28, 34, and 40 hr postinoculation (hpi) (P < 0.05) in the CC piglets. At 28 d postinoculation (dpi), piglets fed P(OA+EO) had a lower (P < 0.05) diarrhea score compared with those fed CC, but the P(OA+EO) piglets had a lower (P < 0.05) diarrhea score compared with those fed the AGP diets at 40 dpi. The ETEC F4 infection tended to increase in vivo gut permeability measured by the oral gavaging fluorescein isothiocyanate-dextran 70 kDa (FITC-D70) assay in the CC piglets compared with the SCC piglets (P = 0.09). The AGP piglets had higher FITC-D70 flux than P(OA+EO) piglets (P < 0.05). The ETEC F4 infection decreased mid-jejunal VH in the CC piglets compared with the SCC piglets (P < 0.05). The P(OA+EO) piglets had higher (P < 0.05) VH in the mid-jejunum than the CC piglets. The relative mRNA abundance of Na+-glucose cotransporter and B0AT1 was reduced (P < 0.05) by ETEC F4 inoculation when compared with the SCC piglets. The AGP piglets had a greater relative mRNA abundance of B0AT1 than the CC piglets (P < 0.05). The ETEC F4 inoculation increased the protein abundance of OCLN (P < 0.05), and the AGP piglets had the lowest relative protein abundance of OCLN among the challenged groups (P < 0.05). The supplementation of microencapsulated OA and EO enhanced intestinal morphology and showed anti-diarrhea effects in weaned piglets challenged with ETEC F4. Even if more future studies can be required for further validation, this study brings evidence that microencapsulated OA and EO combination can be useful within the tools to be implemented in strategies for alternatives to antibiotics in swine production.

Formulations for Allergen Immunotherapy in Human and Veterinary Patients: New Candidates on the Horizon.

Allergen immunotherapy is currently the only causal treatment for allergic diseases in human beings and animals. It aims to re-direct the immune system into a tolerogenic or desensitized state. Requirements include clinical efficacy, safety, and schedules optimizing patient or owner compliance. To achieve these goals, specific allergens can be formulated with adjuvants that prolong tissue deposition and support uptake by antigen presenting cells, and/or provide a beneficial immunomodulatory action. Here, we depict adjuvant formulations being investigated for human and veterinary allergen immunotherapy.

A microencapsulated feed additive containing organic acids, thymol, and vanillin increases in vitro functional activity of peripheral blood leukocytes from broiler chicks.

During the first week after hatch, young chicks are vulnerable to pathogens as the immune system is not fully developed. The objectives of this study were to determine if supplementing the starter diet with a microencapsulated feed additive containing citric and sorbic acids, thymol, and vanillin affects in vitro functional activity of peripheral blood leukocytes (PBLs). Day-old chicks (n = 800) were assigned to either a control diet (0 g/metric ton [MT]) or a diet supplemented with 500 g/MT of the microencapsulated additive. At 4 D of age, peripheral blood was collected (100 birds per treatment), and heterophils and monocytes isolated (n = 4). Heterophils were assayed for the ability to undergo degranulation and production of an oxidative burst response while nitric oxide production was measured in monocytes. Select cytokine and chemokine mRNA expression levels were also determined. Statistical analysis was performed using Student t test comparing the supplemented diet to the control (P ≤ 0.05). Heterophils isolated from chicks fed the microencapsulated citric and sorbic acids, thymol, and vanillin had higher (P ≤ 0.05) levels of degranulation and oxidative burst responses than those isolated from chicks on the control diet. Heterophils from the supplemented chicks also had greater (P ≤ 0.05) expression of IL10, IL1ß, and CXCL8 mRNA than those from control-fed chicks. Similarly, nitric oxide production was significantly (P ≤ 0.05) higher in monocytes isolated from birds fed the supplement. The cytokine and chemokine profile in monocytes from the supplement-fed chicks showed a significant (P ≤ 0.05) drop in IL10 mRNA expression while IL1ß, IL4, and CXCL8 were unchanged. In conclusion, 4 D of supplementation with a microencapsulated blend made up of citric and sorbic acids, thymol, and vanillin enhanced the in vitro PBL functions of degranulation, oxidative burst, and nitric oxide production compared with the control diet. Collectively, the data suggest feeding broiler chicks a diet supplemented with a microencapsulated blend of citric and sorbic acids, thymol, and vanillin may prime key immune cells making them more functionally efficient and acts as an immune-modulator to boost the inefficient and undeveloped immune system of young chicks.

Fraudulent antibiotic products on the market for aquaculture use.

Antibiotics in aquaculture are used to treat bacterial infections. In order for these products to work effectively fish need to be properly dosed. One of the emerging issues in aquaculture is under-dosing large populations of fish with antibiotics. This happens inadvertently for a number of reasons including the use of fraudulent medications. In this study we evaluated 17 antibiotic products (8 florfenicol and 9 oxytetracycline brands purchased in Asia) by HPLC to determine if the product labels accurately reflected the active pharmaceutical ingredient (API) in the package. We determined authenticity scores for different batches of products at two separate laboratories by comparing the observed API to the label API concentration. We found that 48 % of the antibiotic batches had authenticity scores below 80 % (i.e. observed API in package was at least 20 % less than the label API concentration). Further, there were 9 or the 31 batches of drugs tested had no measureable API. Some products had variation in their authenticity scores between batches making it difficult to rely on a brand. The price of florfenicol products may help identify products with low authenticity scores, but in the case of oxytetracycline, the price of all the products tested was relatively similar. The findings in this study suggest that not all florfenicol and oxytetracycline antibiotic products on the market in Asia have API concentrations indicated on their labels. This could be problematic for medicating fish on aquaculture farms.

Copper sulfate and sodium selenite lipid-microencapsulation modifies ruminal microbial fermentation in a dual-flow continuous-culture system.

Undesirable interactions between trace mineral elements and ruminal contents may occur during digestion when mineral salts are supplemented. Antimicrobial effects of copper sulfate (CuSO4) may affect ruminal digestibility of nutrients when fed as a source of copper (Cu), while sodium selenite (Na2SeO3) may be reduced in the rumen to less available forms of selenium (Se). Our objective was to evaluate if protection of CuSO4 and Na2SeO3 by lipid-microencapsulation would induce changes on ruminal microbial fermentation. We used 8 fermentors in a dual-flow continuous-culture system in a 4 × 4 duplicated Latin square with a 2 × 2 factorial arrangement of treatments. Factors were CuSO4 protection (unprotected and protected by lipid-microencapsulation) and Na2SeO3 protection (unprotected and protected by lipid-microencapsulation). Treatments consisted of supplementation with 15 mg/kg of Cu and 0.3 mg/kg of Se from either unprotected or protected (lipid-microencapsulated) sources, as follows: (1) Control (unprotected CuSO4 + unprotected Na2SeO3); (2) Cu-P (protected CuSO4 + unprotected Na2SeO3); (3) Se-P (unprotected CuSO4 + protected Na2SeO3); (4) (Cu+Se)-P (protected CuSO4 + protected Na2SeO3). All diets had the same nutrient composition and fermentors were fed 106 g of dry matter/d. Each experimental period was 10 d (7 d of adaptation and 3 d for sample collections). Daily pooled samples of effluents were analyzed for pH, NH3-N, nutrient digestibility, and flows (g/d) of total N, NH3-N, nonammonia N (NAN), bacterial N, dietary N, and bacterial efficiency. Kinetics of volatile fatty acids was analyzed in samples collected daily at 0, 1, 2, 4, 6, and 8 h after feeding. Main effects of Cu protection, Se protection, and their interaction were tested for all response variables. Kinetics data were analyzed as repeated measures. Protection of Cu decreased acetate molar proportion, increased butyrate proportion, and tended to decrease acetate:propionate ratio in samples of kinetics, but did not modify nutrient digestibility. Protection of Se tended to decrease NH3-N concentration, NH3-N flow, and CP digestibility; and to increase flows of nonammonia N and dietary N. Our results indicate that protection of CuSO4 may increase butyrate concentration at expenses of acetate, while protection of Na2SeO3 tended to reduce ruminal degradation of N. Further research is needed to determine the effects of lipid-microencapsulation on intestinal absorption, tissue distribution of Cu and Se, and animal performance.

Effects of dietary microencapsulated tannic acid supplementation on the growth performance, intestinal morphology, and intestinal microbiota in weaning piglets.

Antibiotics are commonly overused to reduce weaning stress that leads to economic loss in swine production. As potential substitutes of antibiotics, plant extracts have attracted the attention of researchers. However, one of the plant extracts, tannic acid (TA), has an adverse effect on the growth performance, palatability, and intestinal absorption in weaning piglets when used at a large amount. Thus, this study aimed to investigate the effects of a proper dose of microencapsulated TA on the growth performance, organ and intestinal development, intestinal morphology, intestinal nutrient transporters, and colonic microbiota in weaning piglets. Forty-five Duroc × [Landrace × Yorkshire] (initial body weight = 5.99 ± 0.13 kg, weaned days = 21 d) piglets were randomly divided into five treatment groups (n = 9) and raised in 14 d. The piglets in the control group were raised on a basal diet; the piglets in the antibiotic test group were raised on a basal diet with three antibiotics (375 mg/kg Chlortetracycline 20%, 500 mg/kg Enramycin 4%, 1,500 mg/kg Oxytetracycline calcium 20%); and the other three groups were raised on a basal diet with three doses of microencapsulated TA (TA1, 500 mg/kg; TA2, 1,000 mg/kg; TA3, 1,500 mg/kg). All the piglets were raised in the same environment and given the same amount of nutrients for 2 wk. The results showed that both TA1 and TA2 groups had no adverse effect on the growth performance, organ weight and intestinal growth, and the pH value of gastrointestinal content. TA2 treatment improved the duodenal morphology (P < 0.05), increased the gene expression level of solute carrier family 6, member 19 and solute carrier family 15, member 1 (P < 0.05) in the ileum, and modulated the colonic bacteria composition (P < 0.05), but inhibited the activity of maltase in the ileum (P < 0.05) and the jejunal gene expression level of solute carrier family 5, member 1 (P < 0.05). In conclusion, our study suggests that a dosage between 500 and 1,000 mg/kg of microencapsulated TA is safe to be included in the swine diet and that 1,000 mg/kg of microencapsulated TA has beneficial effects on intestinal morphology, intestinal nutrient transporter, and intestinal microbiota in weaning piglets. These findings provide new insights into suitable alternatives to antibiotics for improving growth performance and colonic microbiota.

Preliminary Pilot Study of Itraconazole After a Single Oral Dose of a Veterinary Formulation Solution in African Penguins (Spheniscus demersus).

Aspergillosis is a common cause of morbidity and mortality in captive penguins. Itraconazole, an antifungal drug, is commonly used to treat aspergillosis infections in avian species; however, commercially available human formulations are costly, and studies have shown the effectiveness of compounded formulations to be unreliable. The US Food and Drug Administration (FDA) recently approved a veterinary formulation of itraconazole, Itrafungol, for use in cats. This study provides preliminary results from limited sampling evaluating whether this veterinary formulation is suitable for future studies in the African penguin (Spheniscus demersus). A 20 mg/kg PO itraconazole dose was administered to 9 African penguins. Blood samples were taken over the course of 24 hours; each sample was collected from a different bird to minimize stress to the animals. Plasma was analyzed by high-performance liquid chromatography for concentrations of itraconazole. The drug was absorbed in all penguins, and plasma concentrations in 5 of 9 penguins (56%) were found to be greater than the established therapeutic dose of 1.0 µg/ mL. To our knowledge, this is the first study that has investigated a 20 mg/kg dose of itraconazole in a penguin species. The small sample size limits the conclusions that can be drawn from this preliminary study. Nonetheless, we demonstrate encouraging evidence that the FDA-approved formulation of oral itraconazole solution should be considered for future study as a cost-effective treatment for aspergillosis in African penguins and other avian species.

Randomised clinical non-inferiority trial comparing two formulations of desoxycortone pivalate for the treatment of canine primary hypoadrenocorticism.

BACKGROUND: This clinical trial compared two formulations of desoxycortone pivalate (DOCP) for treating the mineralocorticoid deficit in dogs with primary hypoadrenocorticism (PH). METHODS: At veterinary clinics in the USA and France, dogs with PH (n=152) were randomised (3:1) to receive approximately monthly treatments with either the test product, Zycortal (Dechra), administered subcutaneously (n=113), or the control product, Percorten-V (Novartis Animal Health), administered intramuscularly (n=39), both at an initial dose of 2.2 mg/kg DOCP. Treatment administrators were unblinded; veterinarians assessing clinical signs were blinded; owners were blinded until at least day 90, the primary end point. Veterinarians assessed treatment outcome based on all of the following: clinical signs; sodium concentrations; potassium concentrations. Dogs received concurrent glucocorticoid therapy throughout the trial. Non-inferiority was assessed using a generalised linear mixed model to compare success rates between groups. RESULTS: Success rates at day 90 were similar between groups (per-protocol population at day 90: Zycortal 87/101, 86.2 per cent, Percorten-V 29/34, 85.1 per cent). Zycortal was non-inferior to Percorten-V as the upper limit of the 95 per cent CI for the difference between groups was 13.6 per cent. Polydipsia and polyuria were the most common clinical observations. CONCLUSION: Both products, in combination with glucocorticoid therapy, were safe and effective in treating PH.

Outcome and complications in horses administered sterile or non-sterile fluids intravenously.

BACKGROUND: Obtaining commercial fluids for intravenous administration (IVF) was challenging during a recent shortage. This necessitated use of custom-made non-sterile fluids for intravenous administration (JUGs) in some hospitals. There are no studies comparing outcome of horses treated with JUG versus IVF and limited information is available about adverse effects of JUGs. HYPOTHESIS/OBJECTIVES: To evaluate death, complications, blood pH, and plasma electrolyte concentrations of horses that received JUG versus IVFs. ANIMALS: One hundred eighty-six horses that received IVFs and 37 that received JUGs. METHODS: A retrospective review of medical records was performed to identify horses that received IVFs or JUGs during hospitalization. Information including survival to discharge, complications (fever [>38.5°C], jugular vein phlebitis/thrombosis, arrhythmia, or laminitis), blood pH, and plasma electrolyte concentrations were obtained. RESULTS: There was no difference (P = .67) in survival to discharge for horses that received JUGs (78%) compared to horses that received IVFs (87%). Horses that received JUGs were more likely to develop a jugular vein complication (3 of 37 versus 1 of 186, odds ratio 17.2 [95% CI 1.9-389.8], P = .04). Horses that received JUGs were more likely to have electrolyte abnormalities consistent with hyperchloremic metabolic acidosis. CONCLUSION AND CLINICAL IMPORTANCE: Veterinarians using JUGs should obtain informed client consent because of a potential increased risk of jugular vein complications. Chloride content of JUGs should be considered to limit development of hyperchloremic metabolic acidosis.

Physicochemical and sensory properties of milk supplemented with lactase microcapsules coated with enteric coating materials.

In this paper, we report the physicochemical and sensory properties of milk supplemented with a powder of microencapsulated lactase. The core material was lactase (ß-galactosidase), the primary coating material was medium-chain triglyceride (MCT), and the secondary (enteric) coating material was either hydroxypropyl methylcellulose phthalate (HPMCP) or shellac, comparing both against market milk as a control. The physicochemical properties of both types of microcapsules were analyzed, including the particle size, zeta potential, and in vitro release behavior. To survey the stability of the microcapsules in milk during storage, we studied the residual lactose content and pH. Furthermore, to determine the properties of milk supplemented with the microcapsules, changes in color and sensory properties were evaluated during storage. The particle sizes (volume-weighted mean; D[4,3]) of the microcapsules coated with HPMCP or shellac were 2,836 and 7,834 nm, respectively, and the zeta potential of the capsules coated with shellac was higher than the zeta potential of those coated with HPMCP. The pH levels of milk supplemented with the lactase microcapsules were similar to those of the control (unsupplemented market milk); however, for milk supplemented with HPMCP-coated microcapsules, the pH was slightly lower. The core material, lactase, was released from the microcapsules during 12-d storage, and 18.82 and 35.09% of lactose was hydrolyzed in the samples for HPMCP- and shellac-coated microcapsules, respectively. The sensory characteristics of milk containing microcapsules coated with HPMCP did not show significant differences from the control, in terms of sweetness or off-taste, until 8 d of storage. However, shellac-coated microcapsules showed significant difference in sweetness and off-taste at d 8 and 6 of storage, respectively. The color of milk containing HPMCP-coated microcapsules did not show a significant difference during storage. However, that containing shellac-coated microcapsules was somewhat higher in color values than others. In particular, it showed significance from 0 to 4 d storage in L* and C* values. In conclusion, a powder of lactase microcapsules coated with HPMCP can be suitable as a supplement for milk.

Comparative efficacy of topical treatments with Revolution® Plus (selamectin and sarolaner) and Bravecto® for Cats (fluralaner) against Ixodes scapularis ticks on cats.

The efficacy of three consecutive monthly treatments with a novel topical product (Revolution® Plus/Stronghold® Plus, Zoetis) containing selamectin in combination with the isoxazoline, sarolaner, was compared with that of another topical isoxazoline, fluralaner [Bravecto® (fluralaner topical solution) for Cats, Merck] against Ixodes scapularis ticks on cats. Twenty-four cats were ranked by pre-treatment tick counts to form groups of three and were randomly allocated to be treated with placebo, the minimum label dosage of Revolution® Plus (6 mg/kg selamectin plus 1 mg/kg sarolaner) or the minimum label dosage of Bravecto® for Cats (40 mg/kg fluralaner) within the groups. On Days 0, 30, and 60, each cat in the placebo and Revolution® Plus-treated groups was treated topically, whereas cats in the Bravecto® for Cats-treated group were treated topically once on Day 0 with fluralaner and, subsequently, these animals were treated with the placebo on Days 30 and 60 to maintain masking. Doses were calculated based on weight to provide the minimum label dosage for each product; the calculated volume of product to be administered was rounded off to the nearest 0.1 mL. The selamectin plus sarolaner-treated cats received effective dosages of 5.29-7.12 mg/kg selamectin and 0.88-1.19 mg/kg sarolaner, while the fluralaner cats received dosages of 35.21-43.16 mg/kg fluralaner. Cats were infested with approximately 50 unfed viable adult I. scapularis ticks on Days 5, 12, 26, 40, 54, 68, 82, and 88. Efficacy was assessed at 48 h after each infestation. There were no adverse reactions to any treatment during the study. The placebo-treated cats maintained adequate tick infestations throughout the study. Three monthly treatments with selamectin plus sarolaner (Revolution® Plus) resulted in high and consistent efficacy against I. scapularis for up to 30 days after each treatment. Based on geometric means, efficacy was ≥99.1% at all time points assessed. Treatment with fluralaner (Bravecto® for Cats) provided high and consistent efficacy of ≥99.3% up to Day 70. On Day 84, efficacy was 90.1%; however, cats from which ticks were recovered on Day 84 had received approximately 4%-12% less than the minimum dosage of 40 mg/kg fluralaner. Three consecutive monthly treatments with Revolution® Plus or a single treatment with Bravecto® for Cats provided >90% control of I. scapularis ticks over a 12-week time period.

Efficacy of three consecutive monthly doses of a topical formulation of selamectin and sarolaner (Revolution® Plus/Stronghold® Plus) compared with a single dose of fluralaner (Bravecto® for Cats) against induced infestations of Ctenocephalides felis on cats.

In a controlled laboratory study, the efficacy against fleas, Ctenocephalides felis, of a single treatment of fluralaner topical solution (Bravecto® for Cats, Merck) was compared with that of three consecutive monthly topical treatments with selamectin and sarolaner (Revolution® Plus, Zoetis). Twenty-four domestic short hair cats were ranked based on host suitability flea counts to form groups of three and were randomly assigned within group to one of three treatments. The first group received a topical treatment with (a) placebo (vehicle control for Revolution® Plus) on Days 0, 30, and 60, (b) 6 mg/kg selamectin and 1 mg/kg sarolaner on Days 0, 30, and 60, or (c) 40 mg/kg fluralaner on Day 0 and placebo (vehicle control for Revolution® Plus) on Days 30 and 60. Because doses were rounded off, the selamectin plus sarolaner-treated cats received effective dosages of 5.25-6.60 mg/kg selamectin and 0.88-1.10 mg/kg sarolaner, while the fluralaner-treated cats received dosages of 34.71-43.08 mg/kg fluralaner. All cats were infested with 100 (±5) fleas on Day -1 and at biweekly intervals after that, from Day 13 to Day 89. Flea comb counts were conducted 24 hours after treatment or after re-infestation. There were no adverse events related to treatment during the study. Except for a single cat from which 20 fleas were recovered on Day 90, all other placebo-treated cats had at least 48 fleas at each count, indicating adequacy of infestation of the controls. Based on geometric mean live flea counts, three consecutive monthly treatments with Revolution® Plus resulted in consistent and high efficacy of ≥98.6% compared with placebo throughout the study. A single treatment with Bravecto® for Cats provided consistent and high efficacy of ≥94.6% on all count days during a period of 12 weeks, the approved duration of efficacy for the product. Based on the efficacy results of the study, both products were equivalent in their ability to control fleas on cats. Use of Bravecto® for Cats every 12 weeks or the consecutive monthly use of Revolution® Plus is expected to provide extended high residual kill over the respective labeled durations of efficacy of the two products.

Efficacy and safety of a new topical formulation containing selamectin and sarolaner in the prevention of heartworm disease and the treatment of roundworm infection in cats presented as veterinary patients in Japan.

The efficacy and safety of a new topical formulation containing selamectin plus sarolaner (Revolution® Plus / Stronghold® Plus, Zoetis) was evaluated for the prevention of heartworm (Dirofilaria immitis) disease and the treatment of roundworm infection in cats enrolled as veterinary patients in two field studies conducted in Japan. In the heartworm field study, 91 cats negative for D. immitis antigen and anti-D. immitis antibody were enrolled and received 9 monthly topical treatments with selamectin plus sarolaner during the period of April to December 2015. Efficacy was assessed by testing post-treatment blood samples collected 8, 12, and 15 months after initiation of treatment for the presence of D. immitis antigen and anti-D. immitis antibody. Eighty-seven cats completed the entire study and were included in the determination of efficacy. No D. immitis antigen or anti-D. immitis antibody were detected in any of the post-treatment samples. In the roundworm field study, completed in the period from April to November 2015, 64 cats with ≥100 roundworm eggs per gram (EPG) of feces were enrolled and allocated randomly in a 1:1 ratio, to receive either selamectin plus sarolaner or emodepside plus praziquantel (Profender®, Bayer). Treatments were administered topically on Days 0 and 30, and efficacy was assessed by fecal EPG counts conducted on Days 14, 30, and 60. All cats completed the entire study. At enrollment, all cats were infected with Toxocara cati. Compared to pre-treatment, geometric mean T. cati EPG counts on Days 14, 30, and 60 were reduced by >99.9% in both treatment groups. There were no treatment-related adverse events in either study. Monthly topical administration of Revolution® Plus / Stronghold® Plus providing a minimum of 6 mg/kg selamectin and 1 mg/kg sarolaner was safe and effective in the prevention of heartworm disease and the treatment of roundworm infection in cats enrolled as veterinary patients in Japan.

Preparation, characterization, and in vivo evaluation of a polymorphic form of valnemulin hydrogen tartrate.

We prepared a polymorphic form of valnemulin hydrogen tartrate (Form I) to overcome the instability and irritating odor of valnemulin hydrochloride that affect its use in the production and application of veterinary drugs. The physicochemical properties of Form I were characterized by scanning electron microscopy, X-ray powder diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. The results showed the crystal structure and thermal properties of Form I were very different from those of a commercially available form of valnemulin hydrogen tartrate (Form II). Form I and Form II were more stable than valnemulin hydrochloride after storage under irradiation and high humidity conditions, respectively. The solubility of Form I was 2.6 times that of Form II, and Form I was selected for use in pharmaceutical kinetics experiments in vivo. Compared to valnemulin hydrochloride, after oral administration at a dose of 10 mg/kg in pigs, Form I had similar pharmaceutical kinetic behavior but a slightly higher area under the concentration-time curve from time zero to the last measurable concentration. Consequently, Form I should be suitable for the development of simple formulations and be effective in the clinical application of veterinary drugs.