- Research Article
2
- 10.1016/j.rvsc.2024.105271
Safety of an oral combination of moxidectin, afoxolaner, and pyrantel pamoate in dogs
- Apr 14, 2024
- Research in Veterinary Science
- Marlene Drag + 8 more +8
Publications from 2021 to 2026
Showing 10 of 28 papers
Safety of an oral combination of moxidectin, afoxolaner, and pyrantel pamoate in dogs
Long-term evaluation of viability of microfilariae and intravenously transplanted adult Dirofilaria immitis in microfilaremic dogs treated with low-dose, short- and long-treatment regimens of doxycycline and ivermectin
BackgroundMicrofilarial (mf) counts were monitored over 21.3 months for any rebound that might occur in counts, and adulticidal efficacy was assessed following administration of low dosage with short- and long-treatment regimens of doxycycline and ivermectin to heartworm-microfilaremic dogs.MethodsTwelve heartworm-naïve beagles infected with 10 pairs of adult Dirofilaria immitis by intravenous transplantation were randomly allocated to three groups of four dogs. All treatments started on day 0. On day 0, Group 1 (short-treatment regimen) received doxycycline orally at 10 mg/kg once daily for 30 days plus ivermectin orally (minimum, 6 mcg/kg) on days 0 and 30. Group 2 (long-treatment regimen) received doxycycline orally at 10 mg/kg once daily until individual dogs became mf-negative (72–98 days) and ivermectin every other week until individual dogs became mf-negative (6–7 doses). Group 3 was the untreated control. Mf counts and antigen (Ag) tests were conducted. Dogs were necropsied for recovery and enumeration of heartworms on day 647.ResultsDay −1 mean mf counts were 15,613, 23,950, and 15,513 mf/ml for groups 1, 2, and 3, respectively. Mean counts for Groups 1 and 2 declined until days 239 and 97, respectively, when all were negative. Group 3 had high mf counts throughout the study. There was not a rebound in mf counts in any of the treated dogs after they became amicrofilaremic. All dogs in group 1 and group 3 were Ag-positive throughout the study and had at least one live female worm at necropsy. All dogs in treated Group 2 were positive for Ag through day 154, but were antigen-negative on days 644 and 647, as all had only male worms. Mean live adult worm recoveries for Groups 1, 2, and 3 were 6.8 (range, 5–8), 3.3 (range, 1–6), and 16.0 (range, 14–17), respectively, with a percent reduction in adult worm counts of 57.5% for Group 1 and 79.3% for Group 2.ConclusionsThese data lend support to the use of the American Heartworm Society Canine Guidelines for adulticide therapy recommending the initiation of doxycycline plus a macrocyclic lactone (ML) at the time of the heartworm-positive diagnosis.Graphical
Read morePreventive efficacy of six monthly oral doses of Simparica Trio\xae, Heartgard\xae Plus, and Interceptor\xae Plus against a macrocyclic lactone-resistant strain (ZoeLA) of heartworm (Dirofilaria immitis) in dogs
BackgroundAdministration of four to six consecutive monthly doses of 24 µg/kg moxidectin alone shows high effectiveness in preventing the maturation of macrocyclic lactone (ML)-resistant heartworm strains, Dirofilaria immitis JYD-34 and ZoeLA. This laboratory study evaluated the efficacy of six consecutive monthly oral doses of Simparica Trio® (moxidectin/sarolaner/pyrantel) compared to six monthly doses of either Heartgard® Plus (ivermectin/pyrantel) or Interceptor® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis ZoeLA strain.MethodsBeagle dogs were inoculated with 50 third-stage (L3) D. immitis larvae (ZoeLA) 30 days prior to the first treatment. Dogs were randomized to treatment (six animals in each group) with six monthly oral doses of placebo, Simparica Trio, Heartgard Plus, or Interceptor Plus at their respective label doses. Microfilaria (MF) and antigen tests were conducted periodically, and efficacy was evaluated by necropsy for adult heartworms approximately 9 months after L3 inoculation.ResultsAdult heartworms were recovered from all six placebo dogs, with a geometric mean of 35.5 worms (range, 23–48). Five of the six dogs treated with Simparica Trio were infected with a geometric mean of 1.0 worms (range, 0–3), and all remained MF-negative. All Heartgard Plus-treated dogs (six) were infected with a geometric mean of 32.5 worms (range, 22–38); five of these dogs were MF-positive at day 236. All Interceptor Plus-treated dogs (six) were infected with a geometric mean of 22.8 worms (range, 10–34); five of these dogs were MF-positive at day 236. The efficacy of six consecutive doses with Simparica Trio, Heartgard Plus, and Interceptor Plus against ZoeLA was 97.2, 8.5, and 35.9%, respectively. Adult worm counts for the Simparica Trio-treated group were significantly lower (P < 0.0001) than placebo control, Heartgard Plus, and Interceptor Plus-treated groups. Adult worm counts for Heartgard Plus and Interceptor Plus were not significantly different from placebo (P > 0.05).ConclusionsSimparica Trio prevented microfilaremia in all dogs and was highly effective (97.2%) and significantly better than either Heartgard Plus (8.5%) or Interceptor Plus (35.9%) in preventing the development of the ZoeLA ML-resistant heartworm strain when administered for six consecutive months in this comparative laboratory efficacy study.Graphical
Read moreLaboratory and field studies to investigate the efficacy of a novel, orally administered combination product containing moxidectin, sarolaner and pyrantel for the prevention of heartworm disease (Dirofilaria immitis) in dogs
BackgroundDirofilaria immitis is a filarial parasite of dogs that can cause serious or fatal cardiopulmonary disease. Three studies were conducted to evaluate the efficacy and safety of monthly treatment with moxidectin in a chewable tablet product in combination with sarolaner and pyrantel to prevent heartworm disease in dogs after experimental challenge and in a clinical field study in the USA.MethodsIn two laboratory studies, dogs (8 per group) that had been inoculated 30 days prior with 50 third-stage D. immitis larvae were randomized to treatment on Day 0 with placebo or combination product, at the minimum dose of 24 µg/kg moxidectin, 2 mg/kg sarolaner and 5 mg/kg pyrantel (as pamoate salt). Study 2 also included groups treated with tablets containing moxidectin-alone (24 µg/kg) or sarolaner-alone (2 mg/kg). Efficacy was evaluated ~ 5 months after inoculation by adult heartworm counts at necropsy. In the field study, 410 dogs ≥ 8 weeks-old from 23 USA veterinary clinics were treated for 11 months with either combination product at 24–48 µg/kg moxidectin, 2–4 mg/kg sarolaner and 5–10 mg/kg pyrantel (n = 272) or Heartgard® Plus (ivermectin/pyrantel) at the label recommended dose rate (n = 138). Efficacy was evaluated on Day 330 using antigen and microfilaria testing to assess adult heartworm infection.ResultsIn the laboratory studies, there were no heartworms recovered from any dog treated with the combination product or moxidectin alone and all dogs treated with placebo or sarolaner-alone were infected with 20–44 adult heartworms. In the field study, all dogs treated with the combination product tested negative for heartworm infection on Day 330, whereas two dogs treated with Heartgard® Plus tested positive. The Heartgard® Plus-treated dogs that tested heartworm positive were from the lower Mississippi River Valley region, where heartworm resistance has been confirmed to occur. The combination product was well tolerated in all studies.ConclusionsIn laboratory studies, no heartworms were recovered from dogs treated with a single dose of the novel combination product containing moxidectin, sarolaner and pyrantel. Additionally, in the field study no dog tested positive for adult heartworm infection when dosed with the combination product monthly for 11 months, while two dogs treated with Heartgard® Plus tested positive.
Read moreOptimization of piezoelectric transducer design by modeling and simulation
This work presents the application of Model Based Design (MBD) to optimization of ultrasonic transducer performance using different types of piezoelectric materials, including advanced piezoelectric single crystals PMN-PT and PIN-PMN-PT. The latest trends in MBD were applied for designing and fabrication of different types of transducers - from wideband ultrasonic transducer for bone characterization to 1-3 composite transducers for underwater acoustics.
Read morePhonon localization drives polar nanoregions in a relaxor ferroelectric
Relaxor ferroelectrics exemplify a class of functional materials where interplay between disorder and phase instability results in inhomogeneous nanoregions. Although known for about 30 years, there is no definitive explanation for polar nanoregions (PNRs). Here we show that ferroelectric phonon localization drives PNRs in relaxor ferroelectric PMN-30%PT using neutron scattering. At the frequency of a preexisting resonance mode, nanoregions of standing ferroelectric phonons develop with a coherence length equal to one wavelength and the PNR size. Anderson localization of ferroelectric phonons by resonance modes explains our observations and, with nonlinear slowing, the PNRs and relaxor properties. Phonon localization at additional resonances near the zone edges explains competing antiferroelectric distortions known to occur at the zone edges. Our results indicate the size and shape of PNRs that are not dictated by complex structural details, as commonly assumed, but by phonon resonance wave vectors. This discovery could guide the design of next generation relaxor ferroelectrics.
Read moreRelaxor-PbTiO3 single crystals for various applications.
Piezoelectric materials lie at the heart of electromechanical devices. Applications include actuators, ultrasonic imaging, high intensity focused ultrasound, underwater ultrasound, nondestructive evaluation transducer, pressure sensors, and accelerometers, to name a few. In this work, the advantages and disadvantages of relaxor-PbTiO(3)-based single crystals are discussed, based on the requirements (figure of merit) of various applications, with emphasis on recent developments of the shear properties of single crystals as a function of temperature and applied fields.
Read moreElastic, dielectric and piezoelectric characterization of single domain PIN-PMN-PT: Mn crystals.
Mn modified 0.26Pb(In(1/2)Nb(1/2))O(3)-0.42Pb(Mg(1/3)Nb(2/3))O(3)-0.32PbTiO(3) (PIN-PMN-PT:Mn) single crystals with orthorhombic perovskite crystal structure were polarized along [011] direction, resulting in the single domain state "1O." The complete set of material constants was determined using the combined resonance and ultrasonic methods. The thickness shear piezoelectric coefficient d(15) and electromechanical coupling factor k(15) were found to be on the order of 3100 pC/N and 94%, respectively, much higher than longitudinal d(33) ∼ 270 pC/N and k(33) ∼ 70%. Using the single domain data, the rotated value of d(33)* along [001] direction was found to be 1230 pC/N, in agreement with the experimentally determined d(33) value of 1370 pC/N, conferring extrinsic contributions being about 10%, which was also confirmed using the Rayleigh analysis. In addition, the mechanical quality factors Q(m) were evaluated for different "1O" vibration modes, where the longitudinal Q(m) was found to be ∼1200, much higher than the value for "4O" crystals, ∼300.
Read moreNonlinear capacitors for ESD protection
In order to protect electronic products from Electrostatic Discharge (ESD) damage, multi-layer ceramic capacitors (MLCC) are often used to bypass the transient ESD energy. Most dielectric materials used in MLCC are nonlinear, since the dielectric constant decreases with increasing voltage, reducing the capacitance value, thus degrading the ESD protection effect. Using a large initial capacitance value will ensure sufficient ESD protection; however, the shunt capacitors also limit the signal bandwidth of the ESD-protected data channel, thus setting a maximal capacitance value at data voltage levels. This paper investigates the nonlinearity of capacitors and suggests improved tradeoff between ESD protection and data bandwidth by using the Antiferroelectric (AFE) capacitors as ESD protection. The dielectric constant of AFE material increases with increasing voltage. The voltage dependence of X7R and AFE capacitors are measured using static and nanosecond transient measurements. The ESD protection effectiveness with different material capacitors are compared by simulation. Due to very limited availability of suitable AFE material samples only hand-made capacitors have tested without investigating the long term stability of the material.
Read moreDomain size engineering in tetragonal Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 crystals
The effect of domain size on the dielectric and piezoelectric properties of [111]-oriented tetragonal Pb(In(1∕2)Nb(1∕2))O(3)-Pb(Mg(1∕3)Nb(2∕3))O(3)-PbTiO(3) crystals was investigated. The dielectric permittivity (ɛ(33 ) (T)∕ɛ(0)) and piezoelectric coefficient (d(33)) were found to be on the order of 13 800 and 1630 pC∕N, respectively, for samples with domain size of ∼500 nm, a 3-fold increase to crystals with domain size of ∼50 μm. Rayleigh analysis revealed that the extrinsic contribution to the piezoelectric response increased from ∼8% to 30% with decreasing domain size, due to the increased domain wall density and associated irreversible domain wall motion. The enhanced properties were thought to relate to the fine domain structures, however, showing a poor electric field and temperature stabilities with domain size of 500 nm. Of particular significance is that samples with domain size being on the order of 5 μm exhibit field and temperature stabilities, with yet high piezoelectric properties, make it potential for transducer applications.
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