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Urban trees are at risk of stress due to heat island effects and the increased proportion of impervious areas surrounding them. Among pests of trees, insect borers such as bark beetles (Coleoptera: Curculionidae) and flatheaded borers (Coleoptera: Buprestidae) are some of the most devastating, frequently colonizing stressed trees. The objective of this study was to explore the effects of biotic and abiotic risk factors on borer attacks on trees in urban areas. In the summer of 2021 and 2022, this study was conducted in 50 urban sites in Atlanta and Augusta, Georgia (USA). Specific factors explored include overall tree health, differentially warmer maximum and minimum temperatures of sites compared to surrounding areas, tree species, and the percentage of impervious surface surrounding trees. Generalized linear models and zero-inflated models explored how these factors were related to damage from these borers. The number of borer attacks on trees increased with higher percentage impervious area. As the two most commonly encountered trees, Acer rubrum was found to be significantly more susceptible to attack from borers than Ulmus parvifolia. Unhealthy trees were more likely to experience more frequent and more severe borer attack. Trees with increased impervious cover around them as well as those with differentially warmer daily maximum and minimum temperatures relative to surrounding were more likely to be attacked.

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Exotic ambrosia beetles (Coleoptera: Curculionidae: Scolytinae), such as Xylosandrus crassiusculus (Motschulsky), Xylosandrus germanus (Blandford), and Xylosandrus compactus (Eichoff) are serious pests in southeastern ornamental nurseries. Preventative pyrethroid trunk sprays effectively reduce boring damage. However, it is unclear how pyrethroids such as permethrin prevent attack. Thus, the objective was to determine how permethrin-treated bolts interact with invading ambrosia beetles. In 2022, a study with 2 independent trials was conducted in a nursery on red maple (Acer rubrum L.), bolts during March and April, respectively. The treatments were (i) nonbaited, nontreated bolt, (ii) ethanol baited bolt, (iii) nonbaited bolt + glue [painted on bolt], (iv) ethanol baited bolt + glue, (v) ethanol baited bolt + glue + permethrin, (vi) ethanol baited bolt + glue + permethrin + verbenone, and (vii) ethanol baited bolt + glue + verbenone. Ambrosia beetles trapped on glue, beetles which fell into the pail with soap solution under the bolts, and entry holes on bolts were quantified. Permethrin prevented beetle attacks but did not reduce the number of ambrosia beetles landing on the treated bolts. Verbenone reduced ambrosia beetles from landing on the bolts but did not prevent boring into bolts. The numbers of ambrosia beetles in soapy water were not significantly different among treatments. Ambrosia beetles are landing on permethrin-treated bolts but not boring into the bolts, implying that fresh permethrin residues may not be necessary for ambrosia beetle management.

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PURPOSE: Breast cancer (BC) is a leading cause of morbidity, disability, and mortality in women, worldwide; triple-negative BC (TNBC) is a subtype traditionally associated with poorer prognosis. TNBC special histology subtypes present distinct clinical and molecular features and sensitivity to antineoplastic treatments. However, no consensus has been defined on the best adjuvant therapy. The aim of the review is to study the evidence from literature to inform the choice of adjuvant treatments in this setting. METHODS: We systematically searched literature assessing the benefit of adjuvant chemotherapy in patients with TNBC special histotypes (PROSPERO: CRD42020153818). RESULTS: We screened 6404 records (15 included). All the studies estimated the benefit of different chemotherapy regimens, in retrospective cohorts (median size: 69 patients (range min-max: 17-5142); median follow-up: 51 months (range: 21-268); mostly in Europe and USA). In patients with early-stage adenoid cystic TNBC, a marginal role of chemotherapy was reported. Similar for apocrine TNBC. Medullary tumors exhibited an intrinsic good prognosis with a limited role of chemotherapy, suggested to be modulated by the presence of tumor-infiltrating lymphocytes. A significant impact of chemotherapy on the overall survival was estimated in patients with metaplastic TNBC. Limitations were related to the retrospective design of all the studies and heterogeneous treatments received by the patients. CONCLUSIONS: There is potential opportunity to consider treatment de-escalation and less intense therapies in some patients with early, special histology-type TNBC. International efforts are indispensable to validate prospective clinical decision models.

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Intrauterine exposure to gestational diabetes mellitus (GDM) is linked to development of hypertension, obesity, and type 2 diabetes in children. Our previous studies determined that endothelial colony-forming cells (ECFCs) from neonates exposed to GDM exhibit impaired function. The current goals were to identify aberrantly expressed genes that contribute to impaired function of GDM-exposed ECFCs and to evaluate for evidence of altered epigenetic regulation of gene expression. Genome-wide mRNA expression analysis was conducted on ECFCs from control and GDM pregnancies. Candidate genes were validated by quantitative RT-PCR and Western blotting. Bisulfite sequencing evaluated DNA methylation of placenta-specific 8 (PLAC8). Proliferation and senescence assays of ECFCs transfected with siRNA to knockdown PLAC8 were performed to determine functional impact. Thirty-eight genes were differentially expressed between control and GDM-exposed ECFCs. PLAC8 was highly expressed in GDM-exposed ECFCs, and PLAC8 expression correlated with maternal hyperglycemia. Methylation status of 17 CpG sites in PLAC8 negatively correlated with mRNA expression. Knockdown of PLAC8 in GDM-exposed ECFCs improved proliferation and senescence defects. This study provides strong evidence in neonatal endothelial progenitor cells that GDM exposure in utero leads to altered gene expression and DNA methylation, suggesting the possibility of altered epigenetic regulation.

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PURPOSE: To understand the role of charge in substrate/cyclodextrin complexation by comparing the binding of neutral and charged substrates to a neutral cyclodextrin, such as hydroxypropyl beta-CD (HP-beta-CD) with 3.5 degrees of substitution, and an anionically charged cyclodextrin, such as sulfobutyl ether beta-CD ((SBE)7M-beta-CD) with 6.8 degrees of substitution. METHOD: HP-beta-CD and (SBE)7M-beta-CD were evaluated in their ability to form inclusion complexes with neutral compounds, as well as to cationic and anionic substrates in their charged and uncharged forms. The complexation constants (Kc) were determined via a UV spectrophotometric technique, by monitoring the change in substrate absorbance upon incremental addition of a concentrated cyclodextrin solution. The role of electrostatic interaction was probed by observing Kc as a function of solution ionic strength. RESULTS: Neutral molecules displayed a stronger interaction with (SBE)7M-beta-CD compared to HP-beta-CD. In those cases where the guest possessed a charge (positive or negative), HP-beta-CD/substrate complexes exhibited a decrease in complexation strength (2 to 31 times lower) compared to the neutral forms of the same substrate. The same was true (but to a larger extent, 41 times lower) for negatively charged molecules binding to (SBE)7M-beta-CD due to charge-charge repulsion. However, positively charged molecules interacting with the negatively charged (SBE)7M-beta-CD displayed a similar binding capability as their neutral counterpart, due to charge-charge attraction. Further evaluation through manipulation of solution ionic strength revealed strong electrostatic interactions between substrate and cyclodextrin charges. In addition, the studies suggested that on average two sulfonates out of seven may be involved in forming ionic attraction or repulsion effects with the positive charges on prazosin and papaverine, or negative charges of ionized naproxen and warfarin. CONCLUSIONS: Presence of charge on the cyclodextrin structure provides an additional site of interaction compared to neutral cyclodextrins, which may be modified using solution ionic strength.

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PURPOSE: To understand the role of degree of substitution on binding of molecules to beta-Cyclodextrins (beta-CDs) with varying degrees of sulfobutyl ether (SBE) substitution. METHODS: Using UV spectroscopy, complexation constants of molecules to SBE-beta-CDs were estimated as a function of temperature, allowing for calculation of thermodynamic parameters, including the enthalpy and entropy of binding. RESULTS: Binding constants of various molecules to SBE-beta-CDs did not show a uniform trend to total degree of SBE substitution. However, a distinct pattern was observed with the enthalpy and entropy of complexation. The results showed the complexation of substrates to SBE-beta-CDs to be more entropy-favored as the number of SBE groups increased. This favorable entropy of interaction was compensated by a less favorable enthalpy of interaction. CONCLUSIONS: Enthalpy and entropy of complexation provided additional insight into the role that the alkylsulfonate groups may play in the complexation of molecules with SBE-beta-CDs.

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This review addresses the issue of the mechanisms of drug release from cyclodextrin complexes. More specifically, it attempts to answer the question whether drug release from aqueous formulations is slow or incomplete? A critique of the literature, our own work, and various simulations suggests that drug release from cyclodextrin complexes is rapid and quantitative in most cases. In aqueous solution, drug/cyclodextrin complexes are continually forming and dissociating with lifetimes in the range of milliseconds or less. Although the stronger the binding, the slower the relative kinetics of dissociation, the rates are still fast and essentially instantaneous. After parenteral administration, the major driving force for dissociation of weakly to moderately bound drugs appears to be simple dilution. For strongly bound drugs, binding constants of 10(-4)M(-)(1) or higher, or for those cases where dilution is minimal, contributions from competitive displacement by endogenous materials, drug binding to plasma and tissue components, drug uptake into tissues not available to the complex or the cyclodextrin, rapid elimination of the cyclodextrin and possibly pH and temperature effects, may also be important. After parenteral administration, it does appear that cyclodextrins might cause some alterations in the fraction of free drug eliminated in the urine during that time frame where the cyclodextrin is itself undergoing substantial renal clearance.

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This study was designed to test how the sulfoalkyl ether (SAE) modification of beta-cyclodextrin (beta-CD) affects the binding capacity of testosterone and progesterone, thereby enhancing their solubility. The SAE-beta-CD derivatives contain either sulfopropyl ether (SPE) or sulfobutyl ether (SBE) groups on the 2-, 3-, and 6-hydroxyl positions of the dextrose moieties. SAE-beta-CDs are a mixture of positional and regional isomers containing from one to as many as 12 SAE groups per CD. The effect of chain length and the degree of substitution on complexation behavior was investigated by the phase-solubility method. The results were compared with those obtained with beta-CD, where possible, and with hydroxypropyl-beta-CD (HP-beta-CD). To determine the effect of degree of substitution (DS) on the binding, mixtures of SAE-beta-CDs with multiple substitution levels and varying average degrees of substitution were studied as well as mixtures of SAE-beta-CDs that contained the same degree of substitution. Mixtures that contained SAE-beta-CDs of the same degree of substitution were isolated from the multiple substitution level mixtures by ion-exchange chromatography and purified for investigation. Unlike the parent beta-CD, linear increases in the apparent solubilities of testosterone and progesterone were observed, and the binding potentials were comparable to those of beta-CD or better. The results demonstrate that the binding potentials of the SAE-beta-CD derivatives were dependent on the guest molecule, the degree of substitution, and the alkyl ether chain length. Our previous study showed the inhibition of complexation by direct sulfonation of the beta-CD. However, in the present work, interferences with the charged sulfonate groups were avoided by repositioning them away from the cavity. Increasing the degree of substitution assisted in complex formation; however, its effects were limited. Reduction of the alkyl chain length, as in the case of SPE-beta-CD compared with SBE-beta-CD, decreased the complexation potential. This decrease in complexation potential was further suppressed with an increase in the number of substituents placed on the CD torus. Generally, the binding potential of SAE-beta-CD derivatives increased with increasing alkyl chain length. However, placement of more than an optimum number of SAE groups on the CD torus resulted in inhibition of complexation.

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