Different Modes Of Action Research Articles

Drug resistance and possible therapeutic options against influenza A virus infection over past years.

Influenza A virus infection, commonly known as the flu, has persisted in the community for centuries. Although we have yearly vaccinations to prevent seasonal flu, there remains a dire need for antiviral drugs to treat active infections. The constantly evolving genome of the influenza A virus limits the number of effective antiviral therapeutic options. Over time, antiviral drugs become inefficient due to the development of resistance, as seen with adamantanes, which are now largely ineffective against most circulating strains of the virus. Neuraminidase inhibitors have long been the drug of choice, but due to selection pressure, strains are becoming resistant to this class of drugs. Baloxavir marboxil, a drug with a novel mode of action, can be used against strains resistant to other classes of drugs but is still not available in many countries. Deep research into nanoparticles has shown they are effective as antiviral drugs, opening a new avenue of research to use them as antiviral agents with novel modes of action. As this deadly virus, which has killed millions of people in the past, continues to develop resistance, there is an urgent need for new therapeutic agents with novel modes of action to halt active infections in patients. This review article covers the available therapeutic antiviral drug options with different modes of action, their effectiveness, and resistance to various strains of influenza A virus.

Spectroscopic and chemical characterization of the novel Minocycline/Mn complex with evaluation of its invitro potent antioxidant activity and high antibacterial effect against Escherichia coli (ATCC 8739), Bacillus subtilis (ATCC6633), Staphylococcus aureus (ATCC 6538), and Klebsiella pneumonia (ATCC 13883)

Background and objectiveMinocycline (Mino) is a broad-spectrum antimicrobial that is quickly and fully absorbed. Mino is considered a unique tetracycline derivative. Recently, the number of commercially available antibacterial agents has declined, failing to keep pace with the number of challenges of treating pathogens resistant to multiple drugs. Therefore, it is necessary to develop new classes of antibiotics with different modes of action. Material and methodsThe Mino/manganese (Mino/Mn) complex was synthesized and characterized using elemental analysis, spectroscopic methods (infrared (IR), ultraviolet (UV), X-ray diffraction (XRD)), magnetic susceptibility, scanning electron microscopy SEM, and transmission electron microscopy (TEM). The non-electrolytic nature of the Mino/Mnnovel complex was confirmed based on the molar conductance value. The novel Mino/Mn complex was tested using the ORAC assay and evaluated for its antibacterial activity against the following strains: Escherichia coli (ATCC 8739), Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538), and Klebsiella pneumonia (ATCC 13883). ResultsSpectral data showed that Mino is coordinated with Mn(II) through the oxygen atoms of ketonic (CO) and hydroxyl groups. The magnetic moment value confirms the octahedral configuration of the complex. Surface morphology observed via SEM confirmed that the Mino/Mn novel complex appeared as small rectangular projections. TEM showed the formation of black spots for Mn(II) chelate with particle sizes ranging from 9 to 23 nm. The current findings confirmed the high antibacterial activity of the Mino/Mn complex against the four mentioned strains of bacteria at extremely low concentrations: 0.625 mg/ml for E. coli, 0.009 for B. subtilis, and 0.625 for S. aureus. The Mino/Mn complex exhibited potent antioxidant activity by capturing and scavenging free radicals resulting from antibiotic misuse. ConclusionTherefore, it can be concluded that the novel formula of the Mino/Mn complex is an effective antioxidant and antibacterial agent with expected high potentially significant biological effects.

Molecular Diagnostics for Monitoring Insecticide Resistance in Lepidopteran Pests

Chemical control methods to prevent crop damage have long been directly implicated in the selection of lepidoptera insect populations resistant to insecticides. More recently, new products featuring different modes of action (MoA), developed to mitigate the negative effects of control management on both producers and the environment, are rapidly losing efficacy due to the emergence of insect resistance. Among these, certain resistances are associated with molecular changes in the genomes of pest insects that are valuable for developing molecular markers for diagnostic tools, particularly the point mutations. Molecular diagnosis represents an innovative solution for insecticide resistance management (IRM) practices, allowing for the effective monitoring of insecticide resistance. This approach facilitates decision making by enabling the timely alternation between different modes of action (MoAs). In this context, this review focuses on the major lepidopteran pests that affect globally significant crops, discussing the impacts of insecticide resistance. It gathers literature on diagnostic methods; provides a comparative overview of the advantages of different techniques in terms of efficiency, cost, precision, sensitivity, and applicability; and highlights several novel diagnostic tools. Additionally, this review explores the coffee leaf miner, Leucoptera coffeella, as an applied model to illustrate potential approaches for more effective and sustainable control strategies.

Labor-saving application of thifluzamide and tricyclazole to seedling trays for integrated control of rice blast and sheath blight

Rice blast (Magnaporthe grisea) and sheath blight (Rhizoctonia solani) are limiting factors for rice production. Co-infection of these pathogens results in a disease complex which is difficult to control. In China, growers are accustomed to applying individual fungicides to manage blast and sheath blight, which require large amounts of labor. Application to seedling trays is a new promising solution for saving labor. In this study, application of combined fungicides with different modes of action to seedling trays to integrate control rice blast and sheath blight was evaluated in vitro assays and field trials. The results showed that the combination of thifluzamide and tricyclazole in the 1:2 ratio had significant synergistic inhibitory effects on the mycelial growth of M. grisea and R. solani, with a synergistic ratio (SR) of 2.17 and 1.49. Results from field trials revealed that thifluzamide + tricyclazole at 1107 and 958.5 g/ha applied to seedling trays was the most effective treatment to reduce the disease index of rice blast with control effects of 83.74–84.96% and 81.34–83.26% in 2022 and 2023, respectively, and no significant differences were observed from tricyclazole at 300 g/ha as foliar sprays twice. Compared to the untreated control, disease index of rice sheath blight was notably reduced by all treatments containing thifluzamide. The highest control was recorded in the treatment of thifluzamide + tricyclazole applied at 1107 g/ha to seedling trays. Moreover, compared to the untreated control, all treatments significantly enhanced rice grain yield by 7.67–17.86% and 3.38–18.91% in 2022 and 2023, respectively. The greatest yield (7429.73 and 7404.73 kg/ha in 2022 and 2023, respectively) was observed from the treatment of thifluzamide + tricyclazole at 1107 g/ha applied to seedling trays, with no significant differences among all the treatments containing tricyclazole. Taken together, these results indicated that seedling tray application of thifluzamide + tricyclazole could be a labor-saving approach to the integrated control of rice blast and sheath blight disease complex, while increasing rice grain yield.

Non-Chemical Control of Nymphal Longhorned Tick, Haemaphysalis longicornis Neumann 1901 (Acari: Ixodidae), Using Diatomaceous Earth

The longhorned tick (LHT), Haemaphysalis longicornis Neumann (Acari: Ixodidae), is a serious invasive pest in North America where its geographical range is expanding with high densities associated with commercial animal production. There are only a few chemical pesticides available for LHT control, which can lead to the evolution of resistant strains. Diatomaceous earth (DE) was shown to be effective in killing some important tick species but was not examined for LHTs. When LHT nymphs were dipped for about 2–4 s into DE, transferred to Petri dishes (one tick/dish), and incubated at 30 °C and 70% relative humidity, the median survival time was 4.5 h. A locomotor activity assay showed that there was no difference in the overall distance traveled between the DE-treated and control ticks except during the first 2 h after exposure. In a field-simulated study in which a dose of 5.0 g DE/m2 was applied to pine needle litter infested with LHT, all the LHTs were dead at 24 h with no control mortality. Scanning electron micrographs showed the mineral adhering to all surfaces of the tick. The results indicated that DE is effective in killing nymphal LHTs and could be an alternative to the use of chemical acaricides with the advantage of managing pesticide resistance through the killing by a different mode of action and could be used for organically certified animal husbandry.

Phaleria macrocarpa Fruit Protein Aqueous Extract Affects Viral Entry, Virucidal Activity, and Progeny Release

Presence of acyclovir (ACV) resistant virus posed a major problem in treating virus infection. Alternative treatment with the ability to encounter infection of acyclovir-resistant virus is thus needed and possibly with a different mode of action from ACV. Hence, this study evaluates the antiviral effect of Phaleria macrocarpa (Scheff.) Boerl fruit protein aqueous extract (PMFPAE) against three different strains of human herpesvirus type-1 (HHV-1) including a clinical strain, a less pathogenic strain (KOS-1), and acyclovir (ACV) resistant mutant (UKM-1). PMFPAE displayed antiviral activity towards all the HHV-1 strains when post-treated with high selective indices (SIs) of 80.6, 50, and 35, respectively. Plaque reduction percentages were reduced in attachment and penetration assays following treatment with PMFPAE indicating the ability to deactivate the early phases of the HHV-1 replication cycle. The virucidal activity was also noted following treatment of the virus with PMFPAE and this is supported by damages to the virus envelope as observed by transmission electron microscopy (TEM). Incubation of virus-treated cells with PMFPAE for 24 hr, reduced progeny release in a dose-dependent manner. The study confirms the antiviral mode of action of P. macrocarpa fruit against HHV-1 strains and the ACV-mutant strain includes inhibition during virus entry represented as the early stages of viral replication, virucidal activity, and interfering with progeny release. PMFPAE mode of action is hence different from ACV and worthy for the development of future antiviral drugs.

Insights on the Characteristics and Therapeutic Potential of Mesenchymal Stem Cell-derived Exosomes for Mitigation of Alzheimer's Disease's Pathogenicity: A Systematic Review.

Alzheimer's disease (AD) remains a progressive neurodegenerative disease with no cure. Treatment of AD relies on administering drugs that only subside the symptoms. In recent studies, mesenchymal stem cell (MSC)-exosomes have been marked to possess therapeutic potential for treating AD. This study aims to systematically review and analyse findings that focus on the isolation, characterisation, and sources of MSC-derived exosomes used to unravel the therapeutic potential of these exosomes targeting AD using in vitro and in vivo models. It is hypothesised that MSC-exosomes exhibit high therapeutic potential for AD treatment by exerting various modes of action. PubMed, Scopus, and Medline were used to find relevant published works from January 2016 until December 2020, using assigned keywords including "Alzheimer's disease", "secretome", and "exosomes". Only research articles meeting the predefined inclusion/exclusion criteria were selected and analysed. The risk of bias was assessed using the Office of Health Assessment and Translation tool (OHAT). A total of 17 eligible in vivo and in vitro studies were included in this review. Bone marrow-derived stem cells (BMSCs) were the most used source for exosome isolation, even though studies on exosomes from adipose-derived stem cells (ADSCs) and human umbilical cord stem cells (HUCSCs) provide more information on the characteristics. When the risk of bias was assessed, the studies presented various levels of biases. Notably, the in vitro and in vivo studies revealed neuroprotective properties of MSC-exosomes through different modes of action to alleviate AD pathology. Our review discovered that most MSC exosomes could degrade Aβ plaques, enhance neurogenesis, extenuate neuroinflammatory response through microglial activation, regulate apoptosis and reduce oxidative stress. Delivery of exosomal micro-RNAs was also found to reduce neuroinflammation. Findings from this review provided convincing systematic evidence highlighting the therapeutic properties of MSC-derived exosomes as a prospective source for cell-free (acellular) therapy in treating AD.

Perinatal Caffeine Administration Improves Outcomes in an Ovine Model of Neonatal Hypoxia-Ischemia.

Neonatal hypoxic-ischemic encephalopathy disproportionately affects low- and middle-income countries, where ≈96% of affected infants reside. The current standard of care, therapeutic hypothermia, is frequently ineffective in this setting, likely because injury may be occurring earlier during labor. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal caffeine administration in near-term lambs following global ischemic injury to support the development of earlier treatment strategies targeting the fetus in utero as well as the infant postnatally. Ewes were randomly assigned to receive either 1 g IV caffeine citrate or placebo before delivery and placental transport assessed. Near-term lambs (141-143 days) of both sexes were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Lambs that received caffeine in utero also received 20 mg/kg IV caffeine citrate following resuscitation and 10 mg/(kg·d) IV for 2 days. An additional cohort received 60 mg/kg followed by 30 mg/(kg·d) (low dose versus high dose) postnatally. Biochemical, histological, and neurological outcome measures in lambs were assessed over a 6-day period. Perinatal caffeine administration demonstrated excellent placental transport kinetics and was well tolerated with lamb plasma levels comparable to those targeted in neonates with apnea of prematurity. Caffeine administration resulted in a systemic immunomodulatory effect, evidenced by significant reductions in proinflammatory IP-10 levels. Treated lambs demonstrated improved neurodevelopmental outcomes, while histological analysis revealed that caffeine reduced gray matter injury and attenuated inflammation in the cingulate and parasagittal cortex. This neuroprotective effect was greater and via a different mode of action than we previously reported for azithromycin. A higher caffeine dosing regimen demonstrated significant toxicity. Perinatal caffeine administration is well tolerated, attenuates systemic and brain inflammation, and contributes to improvements in histological and neurological outcomes in an ovine model of neonatal hypoxic-ischemic encephalopathy.

Platinum(II)-Salphen Complexes as DNA Binders and Photosensitisers.

Current anticancer therapies suffer from issues such as off-target side effects and the emergence of drug resistance; therefore, the discovery of alternative therapeutic approaches is vital. These can include the development of drugs with different modes of action, and the exploration of new biomolecular targets. For the former, there has been increasing interest in drugs that are activated by an external stimulus (e. g. light irradiation) to generate cytotoxic chemicals such as reactive oxygen species (ROS). For the latter, significant efforts are being directed to explore non-canonical DNA and RNA structures (e. g. guanine-quadruplexes), as alternative biomolecular targets. Herein we report the synthesis of a library of 21 new platinum(II)-Salphen complexes (square planar platinum(II) complexes coordinated to tetradentate O,N,N,O-Schiff base ligands), and the investigation, for all complexes, of their photophysical and photochemical properties, their interactions with duplex and quadruplex DNA, and their cytotoxicity against HeLa cancer cells both in the dark and upon light irradiation. Thanks to the intrinsic phosphorescence of the platinum(II) complexes, confocal microscopy was used for six of the complexes to determine their cellular permeability and localisation in two cancer cell lines (HeLa and U2OS). Altogether, these studies have allowed us to identify two lead platinum(II) complexes with high guanine-quadruplex DNA affinity and selectivity, good cell permeability and nuclear localisation, and high cytotoxicity against HeLa cancer cells upon irradiation with no detected cytotoxicity in the dark.

A Review on Nanotechnological Approaches for the Management of Stored Insect-Pests: Present Scenario and Future Prospects

Approximately 10% to 30% of the stored agricultural produce is damaged out of which 26% is due to insect-pest infestation thus seriously impacting the food security. The infestation also leads to loss of quality and thereby affecting the overall profitability. In absence of enough storage space, usually farmers dispose-off their produce immediately after harvest and thus do not get remunerative prices. For those opting for storage, physical and chemical methods are in vogue to manage the storage insect-pests. Fumigation with chemical pesticides such as methyl bromide and aluminium phosphide is a common method, though it has its own health and environmental risks. Inhalation of phosphine gas released when aluminium phosphide is used could seriously affect human animal health, sometimes leading to deaths. Thus for using these fumigants, strict supervision of government recognized experts is required. Due to their wide usage, some insect-pests have developed resistance against these molecules. Nanotechnology has created numerous new opportunities in agriculture and allied sectors. Insecticide formulations based on nanotechnology could be a viable alternative to toxic chemicals like aluminium phosphide to manage storage insect-pests. In recent years, a variety of formulations including solid nanopesticides, controlled-release formulations, nano-emulsions, and nano-suspensions have been developed possessing different modes of actions and applications. Their small size is a significant advantage because it provides higher insect-body surface area coverage and thus enhanced efficacy as compared to traditional pesticides. Aside from their small size, they are reported to be safe for non-target beneficial organisms. Nano-pesticides can thus prove as effective and eco-friendly alternatives for insect pest control in storage. However, there is a need to establish their safety on the human and animal ecosystems to rule out their ecological hazards over time. In absence of such information, nanopesticides will not be widely accepted despite their other beneficial effects. In this article, an effort is made to review the current status of nano-formulations for the management of storage-insect-pests, the research and extension gaps and ways to bridge the gaps to ensure safe use of the technology for efficient management of postharvest storage losses.

Synergistic interaction between a toxicant and food stress is further exacerbated by temperature

Global biodiversity is declining at an unprecedented rate in response to multiple environmental stressors. Effective biodiversity management requires deeper understanding of the relevant mechanisms behind such ecological impacts. A key challenge is understanding synergistic interactions between multiple stressors and predicting their combined effects. Here we used Daphnia magna to investigate the interaction between a pyrethroid insecticide esfenvalerate and two non-chemical environmental stressors: elevated temperature and food limitation. We hypothesized that the stressors with different modes of action can act synergistically. Our findings showed additive effects of food limitation and elevated temperature (25 °C, null model effect addition (EA)) with model deviation ratio (MDR) ranging from 0.7 to 0.9. In contrast, we observed strong synergistic interactions between esfenvalerate and food limitation at 20 °C, considerably further amplified at 25 °C. Additionally, for all stress combinations, the synergism intensified over time indicating the latent effects of the pesticide. Consequently, multiple stress substantially reduced the lethal concentration of esfenvalerate by a factor of 19 for the LC50 (0.45–0.024 μg/L) and 130 for the LC10 (0.096–0.00074 μg/L). The stress addition model (SAM) predicted increasing synergistic interactions among stressors with increasing total stress.

A review on synthesis of coumarin derived Schiff’s base metal complexes and their control over E. coli bacterium

Nowadays, the dilemma of drug resistance to antibacterial strains is of huge concern. Among the bacteria, Escherchia coli (E. coli) is the major pathogen, which is found in human and other animals. It is responsible for variety of severe diseases. A variety of commonly used antibiotics such as amoxicillin, gentamycin, etc and fluid replacement method are the suggested treatments for the infections caused by E. coli. In a study, it was established that the metal-based heterocyclic drugs demonstrated a different mode of action compared to the commonly used heterocyclic antibacterial drugs. Coumarin, an oxaheterocycle, is a privileged scaffold in medicinal chemistry. Metal complexes of coumarin-derived Schiff’s bases exhibit a broad range of pharmacological activities. Therefore, in the present review article, we have focused on the synthesis of metal complexes of coumarin derived Schiff’s bases as well as their respective Schiff’s base ligands and their antibacterial activities against the gram-negative bacterium E. coli.

Urea and Thiourea Derivatives of Salinomycin as Agents Targeting Malignant Colon Cancer Cells.

Since it was discovered that a natural polyether ionophore called salinomycin (SAL) selectively inhibits human cancer cells, the scientific world has been paying special attention to this compound. It has been studied for nearly 15 years. Thus, a very interesting research direction is the chemical modification of SAL structure, which could give more biologically active agents. We evaluated the anticancer activity of (thio)urea analogues class of C20-epi-aminosalinomycin (compound 3b). The studies covered the generation of reactive oxygen species (ROS), proapoptotic activity, cytotoxic activity, and lipid peroxidation in vitro. Thioureas 5a‒5d showed antiproliferative activity against selected human colon cancer cell lines greater than that of chemically unmodified SAL, with a 2~10-fold higher potency towards a metastatic variant of colon cancer cells (SW620). Mechanistically, SAL derivatives showed pro-apoptotic activity in primary colon cancer cells and induced the production of reactive oxygen species (ROS) in these cells. In SW620 cells, SAL derivatives increased lipid peroxidation with a weak effect on apoptosis and low ROS formation with cytotoxic effects followed by cytostatic ones, suggesting different modes of action of the compounds against primary and metastatic colon cancer cells. The results of this study suggested that urea and thiourea derivatives of SAL provide promising leads for the rational development of new anticancer active agents.

Insecticide Resistance in Aedes aegypti from the National Capital Region of the Philippines.

Human arboviral diseases such as dengue, chikungunya, and Zika can be transmitted by the mosquito Aedes aegypti. The insecticide-based vector control strategy is critical in reducing transmission of these Aedes-borne diseases but is threatened mainly by the emergence of insecticide resistance. Adult Ae. aegypti from the National Capital Region (NCR), Philippines, were subjected to bioassays to determine their susceptibility to diagnostic doses of pyrethroid, organochlorine, and organophosphate insecticides following the standard World Health Organization insecticide susceptibility test. This study reports the detection of insecticide resistance to pyrethroids and organochlorine in Ae. aegypti from the Philippines for the first time. Most of the Ae. aegypti populations from NCR exhibited phenotypic resistance to permethrin, etofenprox, and DDT. Varying resistance levels to deltamethrin, cyfluthrin, and lambda-cyhalothrin were observed in the different mosquito populations, while all populations tested to malathion were susceptible to this organophosphate. This finding should alert public health authorities to consider modifying the existing vector management package for greater control efficacy. Best practices proven to prevent or delay the development of insecticide resistance, such as insecticide rotation, should also be implemented, while alternative chemicals with a different mode of action should be explored to ensure the continuing efficacy of program interventions.

Experimental evolution under different nutritional conditions changes the genomic architecture and virulence of Acinetobacter baumannii

This study uncovers the molecular processes governing the adaptive evolution of multidrug-resistant (MDR) pathogens without antibiotic pressure. Genomic analysis of MDR Acinetobacter baumannii cells cultured for 8000 generations under starvation conditions (EAB1) or nutrient-rich conditions (EAB2) revealed significant genomic changes, primarily by insertion sequence (IS)-mediated insertions and deletions. Only two Acinetobacter-specific prophage-related deletions and translocations were observed in the EAB1 strain. Both evolved strains exhibited higher virulence in mouse infection studies, each with different modes of action. The EAB1 strain displayed a heightened ability to cross the epithelial barrier of human lung tissue, evade the immune system, and spread to lung tissues, ultimately resulting in cellular mortality. In contrast, the EAB2 strain strongly attached to epithelial cells, leading to increased synthesis of proinflammatory cytokines and chemokines. The genomic alterations and increased virulence observed in evolved strains during short-term evolution underscore the need for caution when handling these pathogens, as these risks persist even without antibiotic exposure.

An Exogenous Ketone Ester Slows Tumor Progression in Murine Breast and Renal Cancer Models.

Ketone esters (KEs) exhibit promise as anti-cancer agents but their impact on spontaneous metastases remains poorly understood. Although consumption of a ketogenic diet (KD) that is low in carbohydrates and high in fats can lead to KE production in vivo, the restrictive composition of KDs may diminish adherence in cancer patients. We investigated the effects of an exogenous ketone ester-supplemented (eKET), carbohydrate-replete diet on tumor growth, metastasis, and underlying mechanisms in orthotopic models of metastatic breast (4T1-Luc) and renal (Renca-Luc) carcinomas. Mice were randomized to diet after tumor challenge. Administration of KEs did not alter tumor cell growth in vitro. However, in mice, our eKET diet increased circulating β-hydroxybutyrate and inhibited primary tumor growth and lung metastasis in both models. Body composition analysis illustrated the overall safety of eKET diet use, although it was associated with a loss of fat mass in mice with renal tumors. Immunogenetic profiling revealed divergent intratumoral eKET-related changes by tumor type. In mammary tumors, Wnt and TGFβ pathways were downregulated, whereas in renal tumors, genes related to hypoxia and DNA damage repair were downregulated. Thus, our eKET diet exerts potent antitumor and antimetastatic effects in both breast and renal cancer models, albeit with different modes of action and physiologic effects. Its potential as an adjuvant dietary approach for patients with diverse cancer types should be explored further.

INSECTICIDE SUSCEPTIBILITY IN TWO POPULATIONS OF Aedes aegypti L. (Diptera: Culicidae) FROM GUERRERO, MEXICO, AND RECOMMENDATIONS FOR THEIR MANAGEMENT

The Aedes aegypti L. mosquito is a vector of diseases such as classic and hemorrhagic dengue (DENV), chikungunya (CHIKV), Zika (ZIKV), yellow fever (YFV), and Mayaro (MAYV). In 2019 alone, in Latin America, there were 2.7 million cases and 1206 deaths. In Mexico, government programs for managing this pest include the elimination of larval habitats and chemical control of larvae and adults. The objective of this study was to evaluate the response of two larvae and adult populations of A. aegypti from the state of Guerrero, Mexico, under laboratory conditions, to insecticides with different modes of action and to make considerations for their management. In the bioassays, larvae showed susceptibility to permethrin, malathion, deltamethrin, and Bacillus thuringiensis var. israelensis; low resistance to Temephos and propoxur; as well as moderate resistance to Spinosad. Both adult populations showed resistance to permethrin and susceptibility to deltamethrin, while the Acapulco population showed resistance to alpha-cypermethrin. For larvae, Spinosad is suggested to be used in times of high incidence of dengue. During drought, it is advisable to include rotations of B. thuringiensis var. israelensis with organophosphates. For adults, the use of imidacloprid in combination with botanical insecticides is considered a rational alternative to rotations with organophosphates and pyrethroids.

The effect of Traumeel LT ad us. vet. on the perioperative inflammatory response after castration of stallions: a prospective, randomized, double-blinded study.

Stallion castration is a standard procedure with a risk of post-surgical complications. Castration induces an acute phase response (APR). Serum Amyloid-A (SAA) is a well-studied major acute phase protein (APP), that has been shown to be a good marker for the development of post-surgical complications. The current gold standard for reducing the APR after castration is Flunixin-Meglumin, which is a non-steroidal anti-inflammatory drug (NSAID) inhibiting COX1/2. In contrast, Traumeel LT ad us. vet. can modulate the APR by induction of the inflammation resolution. The aim of this study was to compare the effect of Flunixin-Meglumin and Traumeel LT ad us. vet. on the acute phase response. A total of 60 stallions were recruited and 54 stallions entered the study with 27 stallions in each treatment group. The stallions were treated pre- and postoperatively with either Flunixin-Meglumin (FL) or with Traumeel LT ad us. vet. (TR). Blood was taken before and 24 h, 48 h and 72 h after castration. The following main parameters were assessed: SAA, fibrinogen, iron, white blood cells, neutrophils, Interleukin1ß, and cortisol. Wound healing and pain were assessed at 8 time points. The main variable SAA was increased after surgery reaching a mean value of 122 µg/ml in the FL group and a mean SAA of 226 µg/ml in the TR group 48 h after surgery, reaching a significant difference only at the 24 h timepoint (p = 0.03). All stallions had the highest pain summary score 8 hours after surgery, with decreasing values thereafter. The pain scores were not statistically different at any time point. In the FL group five stallions developed a suture dehiscence compared to only one stallion in the TR group (p = 0.001). Within the limitations of this study, Traumeel LT ad us. vet. seems to have proresolving effects on the inflammation induced by surgery making it a valuable treatment to reduce the APR induced by castration. Due to its different mode of action, Traumeel LT ad us. vet. might be an alternative treatment option if gastrointestinal side effects or renal side effects of NSAIDs should be avoided. Further studies are needed combining Traumeel LT ad us. vet. and Flunixin.

Multiple Herbicide Resistance in Annual Ryegrass (Lolium rigidum Gaudin) in the Southeastern Cropping Region of Australia

Annual ryegrass (Lolium rigidum) is a problematic weed in winter crops and fallows in the southeastern cropping region (SCR) of Australia. This weed has evolved resistance to multiple herbicide groups, globally. In Australia, L. rigidum is more prevalent in the western and southern regions than in SCR. To assess the herbicide resistance status of L. rigidum, the response of five L. rigidum populations (collected from the SCR) to glyphosate, glufosinate, paraquat, haloxyfop-P-ethyl, and clethodim is determined using dose–response curves. Three parametric logistic models are used to determine the herbicide dose required to achieve 50% survival (LD50) and 50% growth reduction (GR50). The LD50 values for 50% survival at 28 days after treatment range from 1702 g a.e. ha−1 to 8225 g a.e. ha−1 for glyphosate, 1637 g a.i. ha−1 to 1828 g a.i. ha−1 for glufosinate, 141 g a.i. ha−1 to 307 g a.i. ha−1 for paraquat, 11 g a.i. ha−1 to 107 g a.i. ha−1 for haloxyfop-P-ethyl, and 17 g a.i. ha−1 to 48 g a.i. ha−1 for clethodim. The resistance factor, based on GR50 value, is highest in the S7 population (2.2 times) for glyphosate, the S11 population (2.3 times) for glufosinate, the S11 population (2.0 time) for paraquat, the S7 population (3.9 times) for haloxyfop-P-ethyl, and the S3 population (3.1 times) for clethodim, compared with the susceptible or less tolerant population. The S11 population is found to be resistant to five tested herbicides, based on resistance factors. Similarly, the S3 population is highly resistant to glyphosate, haloxyfop-P-ethyl, and clethodim compared with the W4 population. These results suggest that L. rigidum populations in the SCR exhibit resistance to multiple herbicide groups at labelled field rates. The findings highlight the necessity of adopting an integrated management approach, including the use of residual herbicides, tank mixing herbicides with different modes of action, and rotating herbicides in conjunction with cultural and mechanical control methods.

Control of Botrytis cinerea from Chilean grapevines by pydiflumetofen: baseline and carboxamide-mutant sensitivity.

The gray mold (Botrytis cinerea; Botrytis) is the main disease affecting grapevines production in Chile. Succinate Dehydrogenase Inhibitors (SDHI) belonging to the carboxamides fungicide family are a key tool for the control of Botrytis in grapevines from Chilean Central Valley. This study aimed to determine the sensitivity of Chilean Botrytis population to the new generation carboxamide pydiflumetofen. Conidial germination (CG) and germ-tube elongation (GTE) sensitivity assays were conducted on 200 single-spore isolates collected during the 2016-2017 season. The mean effective concentration that inhibited 50% (EC50) of CG in the Botrytis population was 0.0545 µg/mL, with mean values of 0.066 µg/mL and 0.042 µg/mL, for table and wine grapes, respectively. The mean EC50 value of GTE was 0.000245 µg/mL, 0.0003 µg/mL, and 0.0019 µg/mL for the total, table grape, and wine grape populations, respectively. The comparison between pydiflumetofen and fludioxonil, a highly-efficient fungicide carrying a different mode of action, showed the 87.5% and 97.5% of Botrytis control with an EC50 threshold of 0.1 µg/mL, in table grape, and wine grape populations, respectively. No cross-resistance between pydiflumetofen and fludioxonil was detected. For nine isolates with reduced pydiflumetofen sensitivity, we evaluated SdhB mutations using a qPCR-HRM diagnostic system. Two isolates carried the sdhBP225/H272R genotype and two the sdhBP225/H272Y. Additional analysis of SdhB mutant isolates determined that pydiflumetofen controls wild-type as well as sdhBP225/H272R and sdhBP225H/H272 mutants. Pydiflumetofen does not control CG in the sdhBP225/H272Y mutant but is effective in the GTE control. Pydiflumetofen significantly controls Botrytis independently of the SdhB genotype in wounded berry assays. This condition resembles the berry cracking due to heavy rainfall right before harvest, as seen in recent years in the Chilean Central Valley. The findings demonstrate that pydiflumetofen effectively controls the grapevine Botrytis population, suggest a moderate risk of pydiflumetofen resistance, and highlight the significance of incorporating genetic data into the design of control programs.