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Acute lymphoblastic leukemia (ALL) is hematological neoplasia that affects human beings from early life to adulthood. Although ALL treatment has been effective, an important percentage of ALL patients are resilient to treatment. Therefore, there is an urgent need for testing a new combination of compounds for the treatment of this disease. Recently, combined TPEN and TPGS (T2 combo) have shown selective cytotoxic effects in vitro leukemia cells such as Jurkat, K562, and Ba/F3 cells. In this study, we aimed to test the effect of combined TPEN and TPGS agents (T2 combo) at a fixed dose (TPEN 5 mg/kg: TPGS 100 mg/kg) on leukemic Ba/F3-BCR-ABL P210 BALB-c mice model. We found that 4 successive 2-day apart intravenous injections of T2 combo showed a statistically significant reduction of Ba/F3 BCR-ABL leukemia cells (- 69%) in leukemia BALB/c mice (n = 6) compared to untreated leukemia group (n = 6). Moreover, the T2 combo was innocuous to non-leukemia BALB/c mice (n = 3) compared to untreated non-leukemia mice (control, n = 3). After treatments (day 42), all mice were left to rest until day 50. Outstandingly, the leukemia BALB/c mice treated with the T2 combo showed a lower percentage of Ba/F3-BCR-ABL P210 cells (- 84%) than untreated leukemia BALB/c mice. Furthermore, treatment of leukemia and non-leukemia mice with T2 combo showed no significant tissue alteration/damage according to the histopathological analysis of brain, heart, liver, kidney, and spleen samples; however, T2 combo significantly reduced the number of leukocytes in the bone marrow of treated leukemia mice. We conclude that the T2 combo specifically affects leukemia cells but no other tissue/organs. Therefore, we anticipate that the T2 combo might be a potential pro-oxidant combination for the treatment of leukemia patients.

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Eprinomectin and praziquantel, nematodicide and cestodicide compounds, are both combined with the insecticide and acaricide compounds fipronil and (S)-methoprene in Frontline® Protect/Broadline®, or esafoxolaner in NexGard® Combo. These topical feline endectoparasiticide products were tested for efficacy against fleas and intestinal helminths in a field trial in Brazil. Flea- and/or helminth-infested domestic cats were treated twice at a monthly interval following label instructions: 160 cats with Frontline® Protect/Broadline® and 165 cats with NexGard® Combo. The flea and intestinal helminth infestations were evaluated using comb counts and copromicroscopy, respectively before first treatment for baseline value, then 9 and 30 days after each treatment for fleas, and 9 days after each treatment for helminths. Multiparasitism was very frequent at baseline, as amongst the 325 included cats, 295, 280, 86 and 93 cats were at least infested with Ctenocephalides fleas, Ancylostoma, Toxocara and Dipylidium caninum, respectively. Efficacies were calculated by comparing the geometric means at baseline and at post-treatment timepoints for each parasite genus/species. Inclusive of both products and of all evaluation timepoints, the Ctenocephalides, Ancylostoma, Toxocara and D. caninum efficacies were at least 98.3%, 99.8%, 99.8% and 96.3%, respectively. No adverse reactions were observed, except for a few instances of mild, transient, and self-resolving hypersalivation occurring on the day of treatment in both groups. This field trial demonstrated high-level efficacy of Frontline® Protect/Broadline® and NexGard® Combo against major parasites of cats in Brazil.

TITLE: Efficacité de deux produits endectoparasiticides associant fipronil et (S)-méthoprène ou esafoxolaner à l'éprinomectine et au praziquantel contre les puces et les helminthes intestinaux chez les chats naturellement infestés au Brésil. ABSTRACT: L'éprinomectine et le praziquantel, composés nématodicides et cestodicides, sont tous les deux associés aux composés insecticides et acaricides fipronil et (S)-méthoprène dans Frontline® Protect/Broadline®, ou esafoxolaner dans NexGard® Combo. Ces produits endectoparasiticides félins topiques ont été testés pour leur efficacité contre les puces et les helminthes intestinaux lors d'un essai sur le terrain au Brésil. Des chats domestiques infestés de puces et/ou d'helminthes ont été traités deux fois à intervalle d'un mois en suivant les instructions d'utilisation, 160 chats avec Frontline® Protect/Broadline® et 165 chats avec NexGard® Combo. Les infestations par les puces et les helminthes intestinaux ont été évaluées en utilisant respectivement par comptage au peigne et par copromicroscopie, avant le premier traitement pour la valeur de base, puis 9 et 30 jours après chaque traitement pour les puces, et 9 jours après chaque traitement pour les helminthes. Le multiparasitisme était très fréquent à l'inclusion puisque parmi les 325 chats inclus, 295, 280, 86 et 93 chats étaient au moins infestés respectivement par les puces Ctenocephalides, ou Ancylostoma, Toxocara et Dipylidium caninum. Les efficacités ont été calculées en comparant les moyennes géométriques au départ et aux points d'évaluation post-traitement pour chaque genre/espèce de parasite. En incluant les deux produits et tous les points temporels d'évaluation, les efficacités contre Ctenocephalides, Ancylostoma, Toxocara et D. caninum étaient respectivement d'au moins 98,3 %, 99,8 %, 99,8 % et 96,3 %. Aucun effet indésirable n'a été observé à l'exception de quelques cas d'hypersalivation légère, transitoire et auto-résolvante survenant le jour d'un traitement dans les deux groupes. Cet essai sur le terrain a démontré une efficacité de haut niveau de Frontline® Protect / Broadline® et NexGard® Combo contre les principaux parasites des chats au Brésil.

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Glycidyl methacrylate (GMA) and acrylic acid (AAc) were separately grafted onto polypropylene (PP) monofilament sutures by means of pre-irradiation using a (60)Co γ-source, with the purpose of loading vancomycin via (i) covalent immobilization through the glycidyl groups of GMA and (ii) ionic interaction with AAc moieties. The effect of absorbed radiation dose, monomer concentration, temperature and reaction time on the grafting degree was evaluated in detail. GMA grafting ranged from 25% to 800% while the grafting yield of AAc onto PP could be tuned between 9% and 454%, at doses from 5 to 50 kGy and a dose rate 13.7 kGy/h. Grafting of GMA or AAc decreased the decomposition temperature and made the sutures swellable to a certain extent. GMA grafting led to a continuous, smooth and thick coating, which was suitable for immobilization of up to 1.9 µg vancomycin per gram. The immobilized vancomycin enabled a reduction in the Staphylococcus aureus CFU adhered to the suture surface. On the other hand, dried AAc-functionalized sutures exhibited a rough and cracked surface which was responsible for a minor increase in the coefficient of friction. PP-g-AAc sutures exhibited pH-dependent swelling and remarkably high capability to host vancomycin (up to 109.9 mg/g), particularly those with an intermediate degree of grafting. Some AAc-functionalized sutures were shown able to inhibit bacterial growth after successive challenges with fresh lawns. Therefore, tuning the yield of grafting of GMA or AAc may enable the preparation of drug-suture combination products that retain or release, respectively, antimicrobial agents.

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