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Introduction: N -phenyl-2-(aniline) analog N53 is a previously discovered dual inhibitor of Topo I and COX-2, which exhibited significant anti-colon cancer activity in vitro , but the poor solubility and moderate anti-cancer activity in vivo hindered its further development. Methods: To rectify the suboptimal drug properties of N53 , a series of salt forms were developed and further evaluated through in vivo and in vitro experiments. Results: The hydrochloride (N53·HCl) has a well-characterized crystal structure and its solubility reached 540.1 μg/mL, which is nearly 1,700 times higher than that of N53 (0.32 μg/mL). Increasing the N53 solubility consistently promotes its effective concentration, further enhancing the COX-2/Topo I inhibitory activity and the anti-tumor activity in vitro (IC50 values of 2.95 ± 0.08 μM for HT29 cells, 7.99 ± 0.85 μM for RKO cells, 10.94 ± 1.30 μM for HCT116 cells), as well as the anti-proliferative and pro-apoptotic activity. Meanwhile, its oral pharmacokinetic property in vivo is also improved. The elimination half-life (T1/2) is prolonged from 10.78 to 22.29 h, the maximum plasma concentration (Cmax) is increased 2-fold, and the area under the plasma drug concentration-time curve (AUC0–∞) is increased 3-fold. In colon cancer xenograft mouse models, the tumor inhibition rate of N53·HCl was 53.7%, superior to that of N53 (34.7%). Moreover, the results of HE staining showed that N53·HCl had no obvious toxic effects and side effects on other organs, indicating that it was safe in vivo. Discussion: This study demonstrated that N53·HCl exhibits superior pharmacokinetic properties, anti-colon cancer efficacy, and safety, providing a promising drug candidate for colon cancer therapy. [ABSTRACT FROM AUTHOR]

Objectives. Due to Albendazole's relatively low efficacy and bioavailability, Echinococcosis has proven a challenge to manage successfully, with several studies investigating ways to improve the outcome, mainly showing mixed results. We, therefore, aimed to evaluate whether Sulfonated Graphene Oxide (S‐GO), as nanocarriers, could improve the mentioned outcome. Methods. Echinococcus protoscoleces were divided into four groups based on the agent they received, which comprised control, S‐GO, Albendazole, and Albendazole‐loaded S‐GO (S‐GO‐Albendazole). Then, the Bax and Bcl-2 gene expression levels and the number of surviving protoscoleces in each group were determined. Results. Bax gene expression increased by 121% in the 50 μg/ml concentration of the S‐GO‐Albendazole, while Bcl-2 gene expression decreased by 64%. Moreover, S‐GO‐Albendazole was approximately 18% more effective at neutralizing protoscoleces than Albendazole and 14% and 31% more effective at improving the expression of the mentioned genes, respectively (p < 0.05). In addition, the number of surviving protoscoleces after exposure to the mentioned concentration reduced by approximately 99%. Conclusions. S‐GO, despite not having significant lethality on protoscoleces, significantly increased the lethality of Albendazole and, therefore, is a suitable nanocarrier. However, we recommend conducting in vivo and clinical studies to more accurately determine this nanocomplex's potential and side effects. [ABSTRACT FROM AUTHOR]

Copyright of Kocatepe Veterinary Journal / Kocatepe Veteriner Dergisi is the property of Afyon Kocatepe University, Faculty of Veterinary Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Animal Health, Production & Hygiene is the property of Animal Health, Production & Hygiene and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Alveolar echinococcosis (AE), caused by the metacestode of Echinococcus multilocularis, is emerging in both dogs and people in North America. Here, we review 27 cases of canine AE opportunistically reported since the index case was described in 2009 in Western Canada. We describe clinical presentation, diagnosis, treatment, outcome, and source of canine infection, based on genetics of the parasite isolated from some canine cases. Diagnosis of AE was by histopathology and/or PCR on DNA extracted from metacestodes. The median age of dogs at diagnosis was 4 years (range 1–12), which is low compared to neoplasia, the most common differential diagnosis. There was no sex predilection and different breeds were involved, but there were a disproportionate number of boxers and beagles relative to their representation in the general canine population. The most common potential risk factors included contact with wildlife and visits to off leash areas. Abdominal distension was the most common clinical sign at presentation, and medical imaging generally revealed an abdominal mass. On histopathology, protoscoleces were observed in 7 out of 14 dogs. In 7 cases, DNA sequences were most similar to European (versus North American) haplotypes, identical to those recently reported in coyotes as definitive hosts in North America, and different between eastern and western North America, implying multiple introduction events. Dogs that were not treated (n = 6) had 16% survival in the first 100 days in comparison with 82% survival of treated dogs (n = 11). Direct costs to the owner of treating canine AE ranged from 1,317 to 12,655 CAD depending on the situation at the onset of treatment. This study provides important clinical, epidemiological, and economic information for veterinary practitioners and regulators for importation of dogs, and for public health, as dogs with AE may serve as indicators of parasite range expansion and risk to humans. [ABSTRACT FROM AUTHOR]

Copyright of Eurasian Journal of Applied Biotechnology is the property of National Center for Biotechnology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background. Cystic echinococcosis is a zoonotic disease caused by the metacestode stage of Echinococcus granulosus and occurs worldwide, causing considerable economic losses and public health problems. The currently available methods for the diagnosis of animal hydatidosis are time-consuming and require well-equipped laboratories which make them incompatible with testing in resource-poor settings. This study developed and evaluated a rapid, more sensitive, and specific loop-mediated isothermal amplification combined with a lateral flow dipstick assay for the rapid and sensitive detection of cystic echinococcosis. Results. In this study, a specific primer set and FITC-labeled probe targeting the conserved region of the NADH-1 gene were designed. The LAMP reaction was performed at 60°C for 40 minutes, and the amplification products were successfully visualized by LFD strips. The analytical sensitivity of LAMP-LFD was determined using 10-fold serial dilutions of E. granulosus DNA. The minimal concentration detected was 10 fg/μl, and no cross-reactivity was observed with DNA extracted from Taenia solium, Taenia saginata, and Fasciola hepatica. The ability of the developed LAMP-LFD assay to detect cystic echinococcosis was further evaluated with 62 cyst samples from slaughtered cattle in Juja Abattoir, Kiambu County, Kenya. The LAMP-LFD was able to detect 59/62 (95.2%, 95% CI 0.87–0.98) as positive samples of E. granulosus compared to 53/62 (85.5%, 95% CI 0.75–0.92) by nested PCR assay. Conclusion. Our results indicated that the developed LAMP-LFD technique was more sensitive than the nested PCR assay, rapid, and easy to perform with a simple visual detection of products. Therefore, it could be an important point-of-care diagnostic tool for cystic echinococcosis. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the impacts of dietary supranutritional supplementation of selenium-yeast (SY) on growth performance, blood cells, antioxidant status, and metabolic profile of lambs. Twenty-one Kermani male lambs (28.5 ± 2.6 kg of body weight) were used in a completely randomized design for 8 weeks under warm condition with temperature-humidity index (THI) of 81.3 ± 0.37 unit. The lambs were randomly divided into 3 groups given the basal diet either un-supplemented (control group) or supplemented with 0.6 or 1.2 mg of Se/kg dry matter (DM) as SY. Average daily Se intake was 0.12, 0.83, and 1.54 mg in lambs on control, 0.6 mg and 1.2 mg of supplemental Se treatments, respectively (P < 0.0001). The results showed that average daily gain tended to be higher in lambs received Se-supplemented diets than those fed the unsupplemented diet (P < 0.1). Feed efficiency improved by SY supplementation, thereby feed to gain ratio (FG) reduced 19 and 17% respectively in lambs fed 0.6 (FG = 6.58) and 1.2 (FG = 6.7) mg of Se/kg DM compared to those of the control (FG = 8.12) (P < 0.05). Feeding 1.2 mg of Se to growing lambs not only improved blood total antioxidant capacity (T-AOC) as 18.1% and glutathione peroxidase activity (GSH-Px) as 17.6%, but also made 13.1% reduction in serum malondialdehyde (MDA) concentration as a lipid peroxidation marker (P < 0.05). Despite its statistical insignificance (P > 0.05), erythrocyte superoxide dismutase (SOD) activity was also greater in Se-fed groups compared to that of the control. Based on the obtained data, lambs fed 1.2 mg of Se/kg DM, had lower serum urea concentration and albumin to globulin ratio than those on unsupplemented diet (P < 0.05). Moreover, increased RBC count was observed in lambs received 0.6 mg of supplemental Se (P < 0.05). Selenium-enriched yeast supplementation gave rise to increased blood lymphocyte percentage (P < 0.05). The results also indicated that dietary high Se feeding had no adverse effects on blood metabolites including glucose, total protein, albumin, globulin, liver enzymes, and triglyceride content. In the overall, these findings suggest that Se-enriched yeast is a kind of safe Se source for sheep and its dietary supranutritional supplementation for 8 weeks improves feed efficiency of growing lambs. Furthermore, increasing the supplemental Se to 1.2 mg/kg of diet promotes lambs’ blood antioxidant status without inducing any detrimental impacts on cell metabolism. [ABSTRACT FROM AUTHOR]

Antioxidants and oxidative stress status are clinically important in the detection of many diseases. In order to estimate the role of oxidative stress in hydatid disease pathogenesis, the antioxidant levels and oxidative stress status were examined in the patients of hydatid cysts. Thirty patients having active hydatid cyst of Echinococcus granulosus, previously diagnosed by X-ray, were adopted as patients’ group. Additionally, 25 healthy individuals who did not have hydatid infection or any other parasitic infection constituted the control group. Antioxidant status and oxidative stress levels were determined using biochemical tests including plasma Malondialdehyde (MDA) level, and erythrocyte Catalase (CAT), Glutathione Peroxidase (GSH-Px), Superoxide Dismutase (SOD), Glutathione-S-Transferase (GST) activity, in addition to erythrocyte Glutathione concentration GSH-conc. The statistical evaluation of plasma MDA levels showed significantly higher levels in hydatid patients than in healthy controls, while erythrocyte SOD, GSH-Px, CAT, GST and GSH levels were significantly declined in hydatid patients compared to the control which can be used as diagnostic markers in the laboratory diagnosis of the disease. To conclude, hydatid patients show elevated oxidative stress status, and therefore, the antioxidant therapy should be considered in addition to the routine medicines in this group of patients. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the antioxidant and oxidant status of goats naturally infected with Haemonchus contortus. Based upon the parasite burden, infection in goats was categorized as heavy (> 500 worms), mild (100–500 worms) or low (< 100 worms). Abomasal tissues from non-infected and infected goats were used for the determination of catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), aspartate (AST) and alanine (ALT) aminotransferases, acid (ACP) and alkaline (ALP) phosphatases, superoxide content (O2−), protein carbonyl (PC), malondialdehyde (MDA) and reduced glutathione (GSH). A significantly higher level of CAT, GST and GR activity and a lower level of GPx activity were recorded in infected compared to non-infected tissue. A significant increase in the level of AST, ALT, ALP and ACP was found in the abomasal tissue of the infected animals, which was related to the worm burden. The oxidative stress markers were also altered, with a significant decline in GSH levels, whereas MDA, PC and O2− concentrations showed a marked increase. In conclusion, it has been demonstrated that haemonchosis in goats resulted in considerable oxidative stress, which was directly related to the worm burden. [ABSTRACT FROM AUTHOR]

Echinococcus multilocularis is a zoonotic tapeworm of medical and veterinary importance that occasionally infects accidental intermediate hosts causing severe disease or even death. In dogs, alveolar echinococcosis has been reported mainly in central Europe and Canada. The paper presents clinical, biochemical and histological signs of alveolar echinococcosis in a dog from Slovakia and the results of mitochondrial nad1 gene analysis. In 2016, 11-years old Siberian husky female suffering from inappetence was presented to the Veterinary Clinic in Žilina. Biochemical blood examination and blood count showed only minor changes, but abdominal ultrasonography showed the hepatomegaly and the presence of nonhomogeneous hypodense lobulated formation in the left liver lobe. Histological and molecular examinations of excided tissue confirmed the diagnosis of alveolar echinococcosis of the liver. BLAST analysis of E. multilocularis nad1 gene revealed that the nucleotide sequence did not exactly match the previously identified M1 (AJ237639) and/or M2 genotype (AJ237640). In total, two single nucleotide polymorphisms (SNPs) occurred within overlapping region of nad1 gene. In the discussion, clinical and laboratory findings of the infection in other dog patients are compared and the possibilities of diagnosis and therapy of the disease are discussed. [ABSTRACT FROM AUTHOR]

This study examined the relationship between postpartum metritis, reactive oxygen species (ROS) generation, and plasma lipopolysaccharide (LPS) concentration in peripartum dairy cows. Blood was collected twice weekly from 2 weeks prepartum through 6 weeks postpartum. Whole blood chemiluminescence (WBCL) was measured using the luminol-enhanced zymosan-stimulated chemiluminescence assay. Cows were examined for uterine health disorders and classified into two groups, healthy ( n = 11) and metritis ( n = 5). Metritis had a significant effect on WBCL, with cows with metritis having a higher WBCL. Plasma LPS concentrations in cows with metritis were significantly higher than in healthy cows. To examine the effect of LPS on WBCL, blood was sampled in healthy peripartum cows (1 to 2 weeks prepartum, n = 8; 0 to 3 weeks postpartum, n = 11; and 4 to 8 weeks postpartum, n = 8) and incubated with LPS. At 1 endotoxin units/mL of LPS, similar to the plasma LPS concentration in cows with metritis, the WBCL increased in cows at 0 to 3 weeks postpartum. Results indicate that the increase in ROS generation and plasma LPS concentration are associated with metritis, and LPS may be responsible for enhanced ROS generation in early postpartum dairy cows. [ABSTRACT FROM AUTHOR]

Alveolar echinococcosis (AE), a parasitic disease primarily of the liver caused by the larval stage of Echinococcus multilocularis, is highly endemic in Switzerland. In contrast to wellestablished management protocols in people, little is known with regard to optimal treatment strategies in dogs. The objective of this study was to describe the clinical signs and diagnostic procedures in dogs with AE and to evaluate outcome following medical treatment alone or surgery and medical treatment. Of 23 putative AE cases between 2004 and 2014, 20 were classified as confirmed (n=18) or probable (n=2) AE, based on abdominal ultrasound, serology, cytology, histology and/or PCR. Most dogs presented with abdominal distension in an advanced stage of disease. Dogs receiving specific treatment (radical or debulking surgery together with medical treatment, or medical treatment alone) survived longer than dogs left untreated, but no difference was found between treatment types. Survival at one year was associated with absence of free abdominal fluid, absence of abdominal distension and treatment of any type. However, dogs treated with debulking surgery all faced relapse. Findings of this study suggest that in AE-affected dogs for which a therapeutic approach is regarded appropriate by owners and veterinarians, radical surgical resection and medical treatment or, if total resection is not possible, medical treatment alone should be considered. However, studies on larger numbers of dogs are necessary before definitive treatment recommendations can be made. [ABSTRACT FROM AUTHOR]

This article focuses on alveolar echinococcosis (AE), a potentially severe, fatal disease caused by echinococcus multilocularis, a small, zoonotic tapeworm that occurs in various parts of Europe, Eurasia, and North America. Topics discussed include how AE impacts the liver of wild canids and domestic dogs, the paper by Corsini and others (2015) on cases of canine AE in countries such as Switzerland, Germany, and France, and the relevance of the paper to veterinarians in Great Britain.