Herein, we focused on the larvicidal effects and potential mechanisms of 5-ethenyl-2,2'-bithiophene (5 EB), a compound isolated from Echinops ritro L. on Aedes aegypti larvae. Our results show that 5 EB exhibits pronounced larvicidal activity against A. aegypti larvae, with an LC₅₀ = 0.24 mg/L, considerably lesser than that of the traditional insecticide, rotenone. Observations using fluorescence microscopy, electron microscopy, and imaging flow cytometry demonstrated that 5 EB targets the hemocytes of larvae, leading to the disruption of their intracellular membrane systems. This disruption leads to considerable damage to the cellular structure and function, leading to the death of test subjects. Note that additional investigation into the molecular mechanism of 5 EB's action was conducted using transcriptomic analysis. Both GO and KEGG enrichment analyses reported that the differentially expressed genes were predominantly associated with membranes, lysosomes, and catalytic activities. To summarize, this study provides new options for developing new, environmentally friendly, plant-based larvicides for mosquito control.

2024-08-01·Journal of Dairy Science

Evaluating differences in milk production, reproductive performance, and survival associated with vaginal discharge characteristics and fever in postpartum dairy cows

Article

作者: Rosa, G ; Galvão, K N ; Bicalho, R C ; Schuenemann, G M ; Figueiredo, C C ; Zas, S Rodriguez ; Chebel, R C ; Gilbert, R O ; Cunha, F ; Bisinotto, R S ; Santos, J E P ; Thatcher, W W ; Seabury, C M ; Merenda, V R ; Pinedo, P ; de Oliveira, E B ; Casaro, S

The objective was to assess differences in productive and reproductive performance, and survival associated with vaginal discharge characteristics and fever in postpartum dairy cows located in western and southern states of the United States. This retrospective cohort study included data from 3 experiments conducted in 9 dairies. Vaginal discharge was evaluated twice within 12 DIM and scored on a 5-point scale. The highest vaginal discharge score observed for each cow was used to allocate them into 1 of 5 possible groups (VD group) as follows: VD 1 and 2 (VD 1/2; n = 1,174) = clear mucus or lochia with or without flecks of pus; VD 3 (n = 1,802) = mucopurulent with <50% pus; VD 4 (n = 1,643) = mucopurulent with ≥50% of pus or nonfetid reddish-brownish mucus, n = 1,643; VD 5 = fetid, watery, and reddish-brownish, n = 1,800. All VD 5 cows received treatment according to each herd's protocol. Rectal temperature was assessed in a subset of VD 5 cows, and subsequently divided into fever (rectal temperature ≥39.5°C; n = 334) and no fever (n = 558) groups. A smaller proportion of cows with VD 5 (67.6%) resumed ovarian cyclicity compared with VD 1/2 (76.2%) and VD 4 (72.9%) cows; however, a similar proportion of VD 5 and VD 3 (72.6%) cows resumed ovarian cyclicity. A smaller proportion of VD 5 (85.8%) cows received at least one AI compared with VD 1/2 (91.5%), VD 3 (91.0%), or VD 4 (91.6%) cows. Although we did not detect differences in pregnancy at first AI according to VD, fewer cows with VD 5 (64.4%) were pregnant at 300 DIM than cows with VD 1/2 (76.5%), VD 3 (76.2%), or VD 4 (74.7%). Hazard of pregnancy by 300 DIM was smaller for VD 5 compared with VD 1/2, VD 3, or VD 4 cows. A greater proportion of VD 5 cows were removed from the herd within 300 DIM compared with other VD groups. Milk production was 760 kg lower within 300 DIM for VD 5 compared with VD 2, VD 3, and VD 4, whereas VD 2, VD 3, and VD 4 had similar milk production. We did not detect an association between fever at diagnosis of VD 5 and reproductive performance or milk production. A greater proportion of VD 5 cows without fever were removed from the herd by 300 DIM compared with VD 5 cows with fever. Differences in productive and reproductive performance, and removal of the herd were restricted to fetid, watery, and reddish-brownish vaginal discharge, which was independent of fever.

2024-05-01·Journal of Veterinary Pharmacology and Therapeutics

Metronidazole pharmacokinetics in geese (Anser anser domesticus) after intravenous and oral administrations

Article

作者: Fadel, Charbel ; Giorgi, Mario ; Hassoun, Georges ; Poapolathep, Amnart ; Bourdo, Krzysztof ; Łebkowska-Wieruszewska, Beata

AbstractMetronidazole (MTZ) is a 5‐nitroimidazole anti‐bacterial and anti‐protozoal drug. In human and companion animal medicine, MTZ remains widely used due to its effectiveness against anaerobic bacteria and protozoa. In farm animals, however, MTZ is currently prohibited in several countries due to insufficient data on nitroimidazoles. The purpose of this study was to assess its pharmacokinetics (PK) in geese after single intravenous (IV) and oral (PO) administrations. Fifteen‐month old healthy male geese (n = 8) were used. Geese were subjected to a two‐phase, single‐dose (10 mg/kg IV, 50 mg/kg PO), open, longitudinal study design with a two‐week washout period between the IV and PO phases. Blood was drawn from the left wing vein to heparinized tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, and 48 h. Plasma MTZ concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analyzed using PKanalix™ software with a non‐compartmental approach. MTZ was still quantifiable and well above the LLOQ at 24 h after both routes of administration. Following IV administration, terminal elimination half‐life, volume of distribution, and total clearance were 5.47 h, 767 mL/kg, and 96 mL/h/kg, respectively. For the PO route, the bioavailability was high (85%), and the mean peak plasma concentration was 60.27 μg/mL at 1 h. When parameters were normalized for the dose, there were no statistically significant differences for any of the PK parameters between the two routes of administration. The study shows that oral administration of MTZ seems to be promising in geese, although comprehensive research on its pharmacodynamics and multiple‐dose studies are necessary before its adoption in geese can be further considered.

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2023-11-10

·BioSpace

New asundexian Phase III study to include patients with atrial fibrillation ineligible for oral anticoagulant treatment

New study includes patients aged ≥65 years with atrial fibrillation (AF) at high risk for ischemic stroke or systemic embolism who are deemed ineligible for oral anticoagulant (OAC) treatment due to increased risk of bleeding OCEANIC-AFINA, the latest Phase III study in the OCEANIC clinical trial program, will investigate asundexian in this specific patient group OCEANIC-AFINA complements the ongoing OCEANIC-AF study, further expanding Bayer’s landmark clinical trial program with asundexian, enrolling nearly 30,000 patients in over 40 countries Asundexian is being evaluated as a potential improved treatment option in stroke prevention and could be part of an entirely new class of treatment options in thrombosis management WHIPPANY, N.J.--(BUSINESS WIRE)-- Bayer today announced it expanded its Phase III OCEANIC clinical development program for the investigational drug asundexian (BAY2433334) by initiating a third clinical study, OCEANIC-AFINA. OCEANIC AFINA is a Phase III study investigating asundexian as a potential treatment option in patients (≥65 years of age) with atrial fibrillation (AF) at high risk for stroke or systemic embolism who are deemed ineligible for oral anticoagulation (OAC) treatment due to an increased risk of bleeding. OCEANIC-AFINA complements OCEANIC-AF, an ongoing Phase III study investigating the efficacy and safety of asundexian for the prevention of stroke or systemic embolism in people with AF. Together, the results from OCEANIC-AFINA and OCEANIC-AF aim to provide robust evidence for the efficacy and safety of asundexian across a broad range of patients with AF, including those who are at high risk for both ischemic stroke or systemic embolism and major bleeding events. Studies show that 1 in 3 patients with AF are undertreated or untreated with oral anticoagulants, 1,2 leading to a substantial unmet need for an effective therapy that does not further increase the risk of bleeding during treatment. Elderly patients with AF at high risk for bleeding and patients with AF and end-stage kidney disease (ESKD) on hemodialysis are often treated with a lower dose than recommended by guidelines.3 Further, those who discontinue OACs are at increased risk of experiencing a subsequent ischemic stroke.4 Inhibiting FXIa with asundexian might be able to tackle this unmet need, as it could provide protection from thrombotic events without a corresponding increase in bleeding risk. “The promising clinical results we have seen so far indicate that asundexian could mark a new option for antithrombotic treatment for a broader range of patients”, said Dr. Christian Rommel, Member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Global Head of Research and Development. “It is our vision to support patients with atrial fibrillation, including those, that up to now were deemed as not eligible for treatment with OACs. We aim to offer them a new therapy option to help physicians confidently prescribe antithrombotic treatment to protect their patients. With OCEANIC-AFINA we will evaluate asundexian in a vulnerable untreated patient population.” “For physicians, there are challenging clinical decisions we have to make when considering treatment options for atrial fibrillation patients who are at high bleeding risk, and not suitable for currently available oral anticoagulants”, said Dr. Roxana Mehran, Professor of Medicine and Director of Interventional Cardiovascular Research and Clinical Trials at Icahn School at Mount Sinai. “These patients are often overlooked and excluded from clinical trials, so it is gratifying to see Bayer’s announcement of this study.” OCEANIC-AFINA is a multicenter, international, randomized, placebo-controlled, double-blind, parallel-group, 2-arm Phase III study comparing the use of asundexian with placebo in patients (≥65 years of age) with AF at high risk for stroke or systemic embolism who are deemed ineligible to receive treatment with OACs. The primary efficacy objective of OCEANIC-AFINA is to compare the time to first occurrence of ischemic stroke or systemic embolism between AF patients treated with asundexian or placebo. The primary safety objective is to describe the time to first occurrence of ISTH (International Society on Thrombosis and Hemostasis) major bleeding in participants receiving asundexian and placebo.5 The study is expected to enroll nearly 2,000 patients with AF. Asundexian is an investigational agent and has not been approved by any health authority for use in any country, for any indication. It is currently being evaluated as a potential once-daily oral Factor XIa (FXIa) inhibitor for prevention of thromboembolic events, reducing pathological clot formation while allowing hemostasis to form clots to stop the bleeding. About the OCEANIC Program The OCEANIC clinical trial program is designed to evaluate the use of asundexian, as an oral FXIa inhibitor, in patients with atrial fibrillation (AF) at risk of stroke and in patients following acute non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA), aiming to improve the benefit-risk pro compared to standard of care. The program started with two large multinational studies, OCEANIC-AF and OCEANIC-STROKE, and is one of the largest clinical trial programs Bayer has undertaken, expecting to enroll nearly 30,000 patients in over 40 countries. The U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for asundexian as a potential treatment to prevent stroke and systemic embolism in people with atrial fibrillation (AF) as well as for the prevention of stroke in patients after an acute non-cardioembolic ischemic stroke. About OCEANIC-AF, OCEANIC-STROKE and OCEANIC-AFINA OCEANIC-AF is a multicenter, international, randomized, active comparator-controlled, double-blind, double-dummy, parallel-group, 2-arm Phase III study investigating asundexian compared to apixaban (a non-vitamin K antagonist oral anticoagulant) in patients with atrial fibrillation at risk for stroke to determine the safety and efficacy of asundexian on prevention of stroke and systemic embolism. OCEANIC-STROKE is a multicenter, international, randomized, placebo-controlled, double-blind, parallel group and event-driven Phase III study investigating the efficacy and safety of asundexian for prevention of ischemic stroke compared to placebo on top of standard-of-care antiplatelet therapy in patients after an acute non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA) / mini-stroke. OCEANIC-AFINA is a multicenter, international, randomized, placebo-controlled, double-blind, parallel-group, 2-arm Phase III study comparing the use of asundexian with placebo in patients with atrial fibrillation (AF) (≥65 years of age) at high risk for stroke or systemic embolism who are deemed ineligible for OAC treatment. About FXIa inhibitors and Asundexian Factor XI is a protein in the blood which is converted into its active enzyme form (Factor XIa) as part of the blood coagulation cascade. FXIa inhibition specifically targets the FXIa protein involved in pathological thrombus formation, while leaving hemostasis intact. Asundexian, as an oral direct, potent inhibitor of activated coagulation factor XI (FXIa), acts selectively on the coagulation cascade, thereby offering the potential to prevent events like stroke without a corresponding increase in bleeding risk associated with the current standard of care (SoC). Asundexian is currently being evaluated as a potential treatment option in thrombosis prevention and could represent a new approach in antithrombotic treatment. Asundexian is a once-daily, oral investigational agent and has not been approved by any health authority for use in any country, for any indication. About Atrial Fibrillation AF is one of the most common sustained cardiac rhythm disorders (arrhythmias). It results from rapid, disorganized electrical signals in the upper chambers (atria) of the heart, causing them to quiver and contract quickly and irregularly. As a result, the atria do not empty completely, and blood does not flow properly, causing blood clots to form. These blood clots can break loose and travel to the brain, resulting in a stroke.6 About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to . Find more information at Follow us on Facebook: Follow us on Twitter: @BayerPharma Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. References Steinberg BA, Gao H, Shrader P, Pieper K, Thomas L, Camm AJ, Ezekowitz MD, Fonarow GC, Gersh BJ, Goldhaber S, Haas S. International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries. American heart journal. 2017 Dec 1;194:132-40. Steinberg BA, Shrader P, Pieper K, Thomas L, Allen LA, Ansell J, Chan PS, Ezekowitz MD, Fonarow GC, Freeman JV, Gersh BJ. Frequency and Outcomes of Reduced Dose Non–Vita-min K Antagonist Anticoagulants: Results From ORBIT‐AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II). Journal of the American Heart Association. 2018 Feb 16;7(4):e007633. Al-Khatib, S. Pokorney, S. et al. (2020). Underuse of Oral Anticoagulants in Privately Insured Patients with Atrial Fibrillation: A Population Being Targeted by t. Am Heart J. (229), pp.110-117. García Rodríguez, L. et al. (2021). Discontinuation of oral anticoagulation in atrial fibrillation and risk of ischaemic stroke. Heart BMJ. (107), pp.542-548. Bayer AG. OCEANIC-AFINA Study Concept. Data on file. 2023 NHS choices. Atrial fibrillation complications. Available at: . Accessed: November 2023

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