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The objective of this study was to investigate the subharmonic response of Lumason (also known as SonoVue; Bracco, Milan, Italy) to static and dynamic ambient pressures, with a direct comparison to Sonazoid (GE HealthCare, Oslo, Norway) and Definity (Lantheus Medical Imaging, MA, USA). The subharmonic responses of contrast agents can be exploited to perform subharmonic-aided pressure estimation. The subharmonic response of each ultrasound contrast agent was evaluated in both a static and dynamic tank using a commercially available Logiq E10 clinical ultrasound scanner (GE HealthCare) equipped with subharmonic imaging (SHI) and an acoustic power-optimization algorithm. A C1-6 curvilinear array that transmits at 2.5 MHz and receives at 1.25 MHz in SHI mode was used to acquire the subharmonic signals. Data was transferred offline into MATLAB (MathWorks) to perform linear regression analysis and statistical testing for significance of the slopes (i.e. , agent sensitivity). Sonazoid and Definity showed an inverse linear dependency between subharmonic signal and hydrostatic pressure at all pressure ranges (static and dynamic) tested, with maximum sensitivity under 50 mmHg in the static tank (−0.190 and −0.194 dB/mmHg for Sonazoid and Definity, respectively). Lumason exhibited a tri-phasic subharmonic behavior, beginning with a linear trend from 0 to 90 mmHg (sensitivity = 0.069 dB/mmHg), followed by a plateau from 100 to 130 mmHg, and an inverse linear trend from 140 to 200 mmHg (sensitivity = −0.137 dB/mmHg). The subharmonic response of Lumason is tri-phasic and differs from Sonazoid and Definity. Further investigation is needed to solidify understanding of the subharmonic behavior of Lumason to identify its usefulness for subharmonic-aided pressure estimation. [ABSTRACT FROM AUTHOR]

Background: Upper urinary tract stones are increasingly prevalent in pet cats and are difficult to manage. Surgical procedures to address obstructing ureteroliths have short- and long-term complications, and medical therapies (e.g., fluid diuresis and smooth muscle relaxants) are infrequently effective. Burst wave lithotripsy is a non-invasive, ultrasound-guided, handheld focused ultrasound technology to disintegrate urinary stones, which is now undergoing human clinical trials in awake unanesthetized subjects. Results: In this study, we designed and performed in vitro testing of a modified burst wave lithotripsy system to noninvasively fragment stones in cats. The design accounted for differences in anatomic scale, acoustic window, skin-to-stone depth, and stone size. Prototypes were fabricated and tested in a benchtop model using 35 natural calcium oxalate monohydrate stones from cats. In an initial experiment, burst wave lithotripsy was performed using peak ultrasound pressures of 7.3 (n = 10), 8.0 (n = 5), or 8.9 MPa (n = 10) for up to 30 min. Fourteen of 25 stones fragmented to < 1 mm within the 30 min. In a second experiment, burst wave lithotripsy was performed using a second transducer and peak ultrasound pressure of 8.0 MPa (n = 10) for up to 50 min. In the second experiment, 9 of 10 stones fragmented to < 1 mm within the 50 min. Across both experiments, an average of 73–97% of stone mass could be reduced to fragments < 1 mm. A third experiment found negligible injury with in vivo exposure of kidneys and ureters in a porcine animal model. Conclusions: These data support further evaluation of burst wave lithotripsy as a noninvasive intervention for obstructing ureteroliths in cats. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of different injection sites, including dorsal, cheek, and pectoral fin muscles, on the pharmacological properties of amoxicillin (AMOX) in olive flounder (Paralichthys olivaceus) after a single intramuscular (IM) injection of 40 mg/kg. The AMOX concentration was measured using high-performance liquid chromatography-tandem mass spectrometry, followed by a non-compartmental model analysis. The peak serum concentrations (Cmax) achieved 3 h after dorsal, cheek, and pectoral fin IM injections were 202.79, 203.96, and 229.59 μg/mL, respectively. The area under the concentration-time curve (AUC) was 1697.23, 2006.71, and 1846.61 µg/mL·h, respectively. The terminal half-life (t1/2λZ) was prolonged for cheek and pectoral fin IM injections (10.12 and 10.33 h, respectively) compared to dorsal IM injection (8.89 h). In the pharmacokinetic-pharmacodynamic analysis, a higher T > minimum inhibitory concentration (MIC) and AUC/MIC values were observed after AMOX was injected into the cheek and pectoral fin muscles compared to the dorsal muscle. Muscle residue depletion was below the maximum residue level from day 7 after IM injection at all three sites. These findings suggest that the cheek and pectoral fin sites provide advantages regarding systemic drug exposure and prolonged action compared with the dorsal site. [ABSTRACT FROM AUTHOR]

The purpose of this study was to demonstrate the effect of water temperature on residue depletion and withdrawal times (WTs) of tylosin in serum, muscle plus skin, liver, and kidney of the starry flounder, Platichthys stellatus , post oral (PO) administration of tylosin tartrate (TT) at 10 mg/kg dosage for 5 consecutive days. Samples were taken 3, 5, 7, 14, and 21 days post last dose, and tylosin was quantified using liquid chromatography-tandem mass spectrometer (HPLC-MS/MS). The elimination half-life (T 1/2) for each tissue was calculated using ln2/ k and the WT was calculated using the WT 1.4 software at 99% statistical tolerance limit with 95% confidence. High concentrations of tylosin were detected in liver and kidney samples. A decrease in water temperature from 22 to 13 °C prolonged the T 1/2 in all the tissue samples. The T 1/2 were 1.82 and 6.19 d in serum, 2.63 and 3.92 d in muscle plus skin, 4.53 and 13.59 d in liver, and 10.83 and 28.88 d in kidney at 22 and 13 °C, respectively. The WTs for tylosin in the kidney, liver, muscle plus skin, and serum samples were in the following order: 111.7 d > 50.7 d > 20.1 d > 0 d at 22 °C and > 120 d > 81.3 d > 27.9 d > 0 d at 13 °C, respectively. Furthermore, WT (with T 1/2) and water temperature were negatively correlated, in all the tissue samples. Further, our results suggest a WT of 28 d for TT (marker residue; tylosin A) in the muscle plus skin tissue (target tissue) of P. stellatus for its safe consumption. Overall, our study provides a theoretical basis for the effect of water temperature on the drug residue pattern and elimination kinetics of PO administered TT in P. stellatus , which is important for improving food safety in farmed fish. [Display omitted] • Platichthys stellatus were orally administered tylosin at 10 mg/kg for 5 days. • Lower water temperature prolonged tylosin elimination half-life in all the tissues. • Withdrawal time and water temperature negatively correlated for all the tissues. • WT of 28 d recommended for P. stellatus consumption post oral tylosin administration. • Improved understanding of tylosin residue depletion kinetics and WT determination. [ABSTRACT FROM AUTHOR]

Simple Summary: Fishes usually stop eating food when they are sick, and treating diseased fish with oral drugs is a serious hurdle in the aquaculture industry. Tylosin tartrate is a potent bacterial-killing agent useful against frequently occurring bacterial fish infections. We tested the effectiveness against pathogenic bacteria and the human safety of the drug for possible application to cultured olive flounder, one of the most important culture species in far eastern Asian countries. Tylosin tartrate was very effective in killing the pathogenic bacteria grown in artificial culture media, and it was also demonstrated that the drug reached body concentrations in olive flounder, high enough to kill the pathogen. In addition, we also determined how long to wait until the fish clears the injected drug out and it is possible for human consumption. These results will pave a new method for disease treatment useful for olive flounder farming. The objective of this study was to demonstrate the pharmacokinetic–pharmacodynamic profile, bioavailability, and withdrawal time of tylosin tartrate (TT) administered to olive flounder via intramuscular (IM, 10 or 20 mg/kg, n = 240) and intravascular (IV, 10 mg/kg, n = 90) injections. Serum concentrations of tylosin were determined using a validated liquid chromatography-tandem mass spectrometry method. According to the non-compartmental analysis, the bioavailability of TT was 87%. After the IV injection, the terminal half-life, total body clearance, volume of distribution, and mean residence time of TT were 21.07 h, 0.07 L/kg/h, 2.15 L/kg, and 16.39 h, respectively. Rapid absorption (Tmax 0.25 h), prolonged action (terminal half-life, 33.96 and 26.04 h; MRT, 43.66 and 33.09 h), and linear dose–response relationship (AUC0-inf, 123.55 and 246.05 µg/mL*h) were monitored following 10 and 20 mg/kg IM injection. The withdrawal time of TT from muscle (water temperature, 22 °C) was 9.84 days, rounded up to 10 days (220 degree days). Large Cmax/MIC90, AUC0-inf/MIC90, and T > MIC90 values were obtained for Streptococcus isolates and these PK/PD indices satisfied the criteria required for efficacy evaluation. This study lays a foundation for the optimal use of TT and provides valuable information for establishing therapeutic regimens. [ABSTRACT FROM AUTHOR]

Viral hemorrhagic septicemia virus (VHSV) is one of the most important viruses in the aquaculture of farmed finfish. As there is no single solution to prevent or treat VHSV infection, the role of chemical drugs as candidate antiviral agents is indispensable. In this study, we screened 16 coumarin derivatives against VHSV using fathead minnow (FHM) cells by evaluating the cytotoxicity, the inhibition of the VHSV cytopathic effect (CPE) and VHSV N gene expression, respectively. Scoparone (6,7-dimethoxycoumarin), stood out as the most effective compound against VHSV, showing 103.5 ± 10.2 μg/mL 20% cytotoxicity (CC 20), 40% CPE reduction and 9.8-fold (P < 0.001) VHSV N gene inhibition at 100 μg/mL. Scoparone, at 100 μg/mL inhibited the VHSV infection by 1-h postinfection treatment, with 52.0% ± 17.1% plaque reduction (P < 0.05), and 90.6% VHSV N gene inhibition (P < 0.05) indicating it inhibits viral internalization and replication. Scoparone exhibited direct virucidal activity, increasing with exposure period, up to 32.3% ± 1.3% plaque reduction from 4 h incubation (P < 0.001), indicating its reversible nature. Scoparone-medicated feed protected the fish from VHSV infection, with up to 44% relative percent survival by 1 mg (long-term) and 10 mg (short-term) prophylactic administration per kg body weight (bw) per day for 21 and 7 days, respectively, in the olive flounder Paralichthys olivaceus. No negative effects were noted on the growth, biochemical, or innate immunological parameters of the fish administered up to 3 mg/kg bw/day of scoparone-medicated feed for 28 days. The administration of scoparone-medicated feed at 1 mg/kg bw/day for 14 days and subsequent VHSV challenge decreased VHSV N gene expression by 48 h postinfection (hpi) in olive flounders. Increased expression levels of IFN I and ISG15 suggested the pivotal role of the IFN I system in conferring scoparone-mediated protection against VHSV infection. The activation of MDA5 at 48 hpi must be attributed to the elevated interferon activity. Elevated interferon type II expression levels suggested the induction of adaptive immune responses. The expression of TLR2 was suppressed at 72 hpi, reflecting reduced viral replication by scoparone. The suppressed expression of caspase 3 suggested that scoparone inhibits virus-induced apoptosis. In summary, scoparone can be considered a practical candidate for protecting farmed finfish against VHSV. It can protect olive flounders from VHSV infection through multiple mechanisms of action and by a convenient mode of administration via medicated feed. [Display omitted] • Scoparone inhibits replication of VHSV in vitro and in vivo. • Scoparone has direct virucidal activity against VHSV. • Scoparone-medicated feed has prophylactic effect against VHS in olive flounder. • Scoparone activates IFN I system upon VHS infection. [ABSTRACT FROM AUTHOR]

The whitening effect of reducing skin pigmentation is one of the most important goals of cosmetics. The purpose of this study was to determine whether Catalpa ovata extract and its fractions have potential as natural skin-lightening agents. Initially, we screened various fractions of Catalpa ovata extract using an in vitro antioxidant assay. Then, the inhibitory effects of C. ovata extract and its fraction on melanogenesis and the related mechanisms were investigated in B16F1 melanoma cells. The results showed that the ethyl acetate fraction (EF) from C. ovata extract markedly inhibited melanin synthesis in a dose-dependent manner at non-toxic concentrations. Furthermore, EF downregulated both the protein and mRNA levels of tyrosinase, which is a specific enzyme that catalyzes the conversion of tyrosine into melanin. We also found that EF decreased the microphthalmia-associated transcription factor (MITF) at the protein and mRNA levels. EF increased the phosphorylation of ERK and suppressed the phosphorylation of JNK and p38 in ɑ-MSH-induced B16F1 cells. These results indicate that EF can regulate the MAPK pathway. In addition, EF has an anti-melanogenic effect via the downregulation of intracellular cyclic-AMP (cAMP). Nineteen major compounds of EF were identified using LC-MS/MS. Taken together, these results suggest that EF may be a potential anti-melanogenic agent for use in skin-whitening cosmetics and in topical treatments for hyperpigmentation disorders. [ABSTRACT FROM AUTHOR]

The most common neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD) and Parkinson's disease (PD), are the seventh leading cause of mortality and morbidity in developed countries. Clinical observations of NDD patients are characterized by a progressive loss of neurons in the brain along with memory decline. The common pathological hallmarks of NDDs include oxidative stress, the dysregulation of calcium, protein aggregation, a defective protein clearance system, mitochondrial dysfunction, neuroinflammation, neuronal apoptosis, and damage to cholinergic neurons. Therefore, managing this pathology requires screening drugs with different pathological targets, and suitable drugs for slowing the progression or prevention of NDDs remain to be discovered. Among the pharmacological strategies used to manage NDDs, natural drugs represent a promising therapeutic strategy. This review discusses the neuroprotective potential of seaweed and its bioactive compounds, and safety issues, which may provide several beneficial insights that warrant further investigation. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment is a typical symptom of early Alzheimer's disease (AD). Glehnia littoralis (G. littoralis), a medicinal halophyte plant commonly used to treat strokes, has been shown to possess some therapeutic qualities. In this study, we investigated the neuroprotective and anti-neuroinflammatory effects of a 50% ethanol extract of G. littoralis (GLE) on lipopolysccharide (LPS)-stimulated BV-2 cells and scopolamine-induced amnesic mice. In the in vitro study, GLE treatment (100, 200, and 400 µg/mL) markedly attenuated the translocation of NF-κB to the nucleus concomitantly with the significant mitigation of the LPS-induced production of inflammatory mediators, including NO, iNOS, COX-2, IL-6, and TNF-α. In addition, the GLE treatment suppressed the phosphorylation of MAPK signaling in the LPS-stimulated BV-2 cells. In the in vivo study, mice were orally administered with the GLE (50, 100, and 200 mg/kg) for 14 days, and cognitive loss was induced via the intraperitoneal injection of scopolamine (1 mg/kg) from 8 to 14 days. We found that GLE treatment ameliorated memory impairment and simultaneously improved memory function in the scopolamine-induced amnesic mice. Correspondingly, GLE treatment significantly decreased the AChE level and upregulated the protein expression of neuroprotective markers, such as BDNF and CREB, as well as Nrf2/HO-1 and decreased the levels of iNOS and COX-2 in the hippocampus and cortex. Furthermore, GLE treatment attenuated the increased phosphorylation of NF-κB/MAPK signaling in the hippocampus and cortex. These results suggest that GLE has a potential neuroprotective activity that may ameliorate learning and memory impairment by regulating AChE activity, promoting CREB/BDNF signaling, and inhibiting NF-κB/MAPK signaling and neuroinflammation. [Display omitted] • GLE can inhibit the over activation of BV-2 cells by reducing the release of NO and inflammatory factors. • GLE can play an anti-inflammatory role through MAPK/NF-κB signaling pathways induced by LPS. • GLE reversed memory impairment through enhancing BDNF/CREB expression in scopolamine-induced C57BL/6 mouse model. • GLE prevents oxidative stress by regulating Nrf-2/HO-1 expression in scopolamine-induced C57BL/6 mouse model. [ABSTRACT FROM AUTHOR]

Injectable antibiotics have some advantages over oral administration under certain conditions. However, they have not been adopted actively, especially in the aquaculture field. Here, we focused on the effect of intramuscular (i.m.) injection of lincomycin HCl (LH), a lincosamide antibiotic, on a streptococcal infection in olive flounders (Paralichthys olivaceus). In-vitro efficacy tests with 49 Streptococcus parauberis clinical isolates revealed inhibition of 32 isolates (65.3%) by 2 μg/mL LH, as the 50% minimum inhibitory concentration (MIC 50). A single LH i.m. injection (10 mg/kg) in-vivo significantly reduced cumulative mortality rates against S. parauberis infection from 100% to 0–20.0% (P < 0.0001). For pharmacokinetic analysis, LH concentrations in serum and muscle were monitored after single i.m. injection of LH (10 and 20 mg/kg). The peak serum concentration (C max) was 22.45 μg/mL (time to peak serum, T max , 0.25 h) and C max was 27.40 μg/mL (T max , 0.5 h) after a single i.m. dose of 10 and 20 mg/kg, respectively, with the two doses leading to large C max /MIC 50 and T > MIC 50 (time period remained above MIC 50) values against S. parauberis. After intravenous injection, the volume of distribution (V z) was high in olive flounder (2.44 L/kg). LH bioavailability was 88.99% following a single i.m. injection of 10 mg/kg. Analyses of muscle residue depletion demonstrated appropriate withdrawal times of 19.95 days (99% statistical tolerance limit) after a single 10 mg/kg i.m. injection. Overall, our results suggest that a single i.m. injection of LH at 10 mg/kg offers acceptable efficacy with reasonable withdrawal periods for streptococcal infection in olive flounder. • Lincomycin HCl (LH) at 10 mg/kg is effective against Streptococcus parauberis in olive flounder. • Clinical doses of LH will not affecting food safety standards. • Utilization of injectable single dose LH is clinically feasible in fish species. [ABSTRACT FROM AUTHOR]

Injectable antibiotics have some advantages over oral administration under certain conditions. However, they have not been adopted actively, especially in the aquaculture field. Here, we focused on the effect of intramuscular (i.m.) injection of lincomycin HCl (LH), a lincosamide antibiotic, on a streptococcal infection in olive flounders (Paralichthys olivaceus). In-vitro efficacy tests with 49 Streptococcus parauberis clinical isolates revealed inhibition of 32 isolates (65.3%) by 2 μg/mL LH, as the 50% minimum inhibitory concentration (MIC 50). A single LH i.m. injection (10 mg/kg) in-vivo significantly reduced cumulative mortality rates against S. parauberis infection from 100% to 0–20.0% (P < 0.0001). For pharmacokinetic analysis, LH concentrations in serum and muscle were monitored after single i.m. injection of LH (10 and 20 mg/kg). The peak serum concentration (C max) was 22.45 μg/mL (time to peak serum, T max , 0.25 h) and C max was 27.40 μg/mL (T max , 0.5 h) after a single i.m. dose of 10 and 20 mg/kg, respectively, with the two doses leading to large C max /MIC 50 and T > MIC 50 (time period remained above MIC 50) values against S. parauberis. After intravenous injection, the volume of distribution (V z) was high in olive flounder (2.44 L/kg). LH bioavailability was 88.99% following a single i.m. injection of 10 mg/kg. Analyses of muscle residue depletion demonstrated appropriate withdrawal times of 19.95 days (99% statistical tolerance limit) after a single 10 mg/kg i.m. injection. Overall, our results suggest that a single i.m. injection of LH at 10 mg/kg offers acceptable efficacy with reasonable withdrawal periods for streptococcal infection in olive flounder. • Lincomycin HCl (LH) at 10 mg/kg is effective against Streptococcus parauberis in olive flounder. • Clinical doses of LH will not affecting food safety standards. • Utilization of injectable single dose LH is clinically feasible in fish species. [ABSTRACT FROM AUTHOR]