Acridine derivatives have been found with anticancer and antinociceptive activities. Herein, we aimed to evaluate the toxicological, antitumor, and antinociceptive actions of ...N’-(6-chloro-2-methoxyacridin-9-yl)-2-cyanoacetohydrazide (ACS-AZ), a 9-aminoacridine derivative with antimalarial activity. The toxicity was assessed by acute toxicity and micronucleus tests in mice. The
in vivo
antitumor effect of ACS-AZ (12.5, 25, or 50 mg/kg, intraperitoneally, i.p.) was determined using the Ehrlich tumor model, and toxicity. The antinociceptive efficacy of the compound (50 mg/kg, i.p.) was investigated using formalin and hot plate assays in mice. The role of the opioid system was also investigated. In the acute toxicity test, the LD
50
(lethal dose 50%) value was 500 mg/kg (i.p.), and no detectable genotoxic effect was observed. After a 7-day treatment, ACS-AZ significantly (
p
< 0.05) reduced tumor cell viability and peritumoral microvessels density, suggesting antiangiogenic action. In addition, ACS-AZ reduced (
p
< 0.05) IL-1β and CCL-2 levels, which may be related to the antiangiogenic effect, while increasing (
p
< 0.05) TNF-α and IL-4 levels, which are related to its direct cytotoxicity. ACS-AZ also decreased (
p
< 0.05) oxidative stress and nitric oxide (NO) levels, both of which are crucial mediators in cancer known for their angiogenic action. Moreover, weak toxicological effects were recorded after a 7-day treatment (biochemical, hematological, and histological parameters). Concerning antinociceptive activity, ACS-AZ was effective on hotplate and formalin (early and late phases) tests (
p
< 0.05), characteristic of analgesic agents with central action. Through pretreatment with the non-selective (naloxone) and μ1-selective (naloxonazine) opioid antagonists, we observed that the antinociceptive effect of ACS-AZ is mediated mainly by μ1-opioid receptors (
p
< 0.05). In conclusion, ACS-AZ has low toxicity and antitumoral activity related to cytotoxic and antiangiogenic actions that involve the modulation of reactive oxygen species, NO, and cytokine levels, in addition to antinociceptive properties involving the opioid system.
This paper presents a framework to support decision-making in aircraft conceptual design optimisation under uncertainty. Emphasis is given to graphical visualisation methods capable of providing ...holistic yet intuitive relationships between design, objectives, feasibility and uncertainty spaces. Two concepts are introduced to allow interactive exploration of the effects of (1) target probability of constraint satisfaction (price of feasibility robustness) and (2) uncertainty reduction through increased state-of-knowledge (cost of uncertainty) on design and objective spaces. These processes are tailored to handle multi-objective optimisation problems and leverage visualisation techniques for dynamic inter-space mapping. An information reuse strategy is presented to enable obtaining multiple robust Pareto sets at an affordable computational cost. A case study demonstrates how the presented framework addresses some of the challenges and opportunities regarding the adoption of Uncertainty-based Multidisciplinary Design Optimisation (UMDO) in the aerospace industry, such as design margins policy, systematic and conscious definition of target robustness and uncertainty reduction experiments selection and prioritisation.
The last few decades have seen a notable increase in the number of people who have a tattoo. This practice is not free from complications. Most adverse effects appear early and are temporary, ...although they can occasionally develop later and be permanent and serious. Recent research has generated new knowledge on the composition of inks, their degradation over time, the immune activity that is stimulated, and the various clinical disorders that can arise. This information enables better approaches to diagnosis and management when complications arise. Diagnosing allergic reactions to permanent tattoo ink can be very challenging. This review aims to identify clinical and histological clues to help practitioners differentiate allergic reactions from other complications. We discuss the yield and appropriateness of skin tests and biopsies and propose an algorithm to guide the diagnostic process.
The high producing dairy cow of the 21st century is subfertile during lactation. Our objectives are to characterize physiological periods limiting reproductive performance and to describe integrated ...management strategies to improve pregnancy rates. Ovarian recrudescence with normal re-occurring estrous cycles and restoration of fertility to first service are associated with a reduced occurrence of periparturient metabolic and reproductive disorders. Marked negative changes in energy balance and reduced immunocompetence influence gonadotropic and metabolic hormones. Induced ovarian inactivity was associated with enhanced uterine involution. Post-partum health and reproductive performance were improved when by-pass lipids enriched in polyunsaturated fatty acids were fed in the pre- and post-partum periods. Pharmaceutical control of follicle, CL, and uterine function with PGF, GnRH and intravaginal progesterone releasing inserts, has permitted development of more optimal timed-insemination programs for first service. Likewise, resynchronization of nonpregnant cows coupled with the use of ultrasound for early pregnancy diagnosis provides the opportunity for a second timed-insemination within 3 days of a nonpregnant diagnosis. Bovine somatotropin (bST) increases embryo development and embryo survival when coupled with a timed-insemination program or cows detected in estrus. Presence of a conceptus alters endometrial expression of genes and proteins in response to bST and nutraceuticals (i.e., unsaturated fatty acids such as eicosapentaenoic and docosahexaenoic acid in by-pass lipids) to improve pregnancy rates. Postovulatory increases in progesterone may enhance pregnancy rates in targeted populations of lactating dairy cows, but timing and magnitude of the progesterone increases are pharmaceutically dependent.
The present study was carried out to evaluate the possible association between obesity and periodontitis in patients with DS, and to explore which measure of obesity is most closely correlated to ...periodontitis.
A prospective observational study was made to determine whether obesity is related to periodontal disease in patients with DS. The anthropometric variables were body height and weight, which were used to calculate BMI and stratify the patients into three categories: < 25(normal weight), 25-29.9 (overweight) and ≥ 30.0 kg/m2 (obese). Waist circumference and hip circumference in turn was recorded as the greatest circumference at the level of the buttocks, while the waist/hip ratio (WHR) was calculated. Periodontal evaluation was made of all teeth recording the plaque index (PI), pocket depth (PD), clinical attachment level (CAL) and the gingival index. We generated a multivariate linear regression model to examine the relationship between PD and the frequency of tooth brushing, gender, BMI, WHI, WHR, age and PI.
Significant positive correlations were observed among the anthropometric parameters BMI, WHR, WHI and among the periodontal parameters PI, PD, CAL and GI. The only positive correlation between the anthropometric and periodontal parameters corresponded to WHR. Upon closer examination, the distribution of WHR was seen to differ according to gender. Among the women, the correlation between WHR and the periodontal variables decreased to nonsignificant levels. In contrast, among the males the correlation remained significant and even increased. In a multivariate linear regression model, the coefficients relating PD to PI, WHR and age were positive and significant in all cases.
Our results suggest that there may indeed be an association between obesity and periodontitis in male patients with DS. Also, we found a clear correlation with WHR, which was considered to be the ideal adiposity indicator in this context.
Periodontitis has been regarded as a potential risk factor for rheumatoid arthrosis (RA). A systematic review is made to determine whether nonsurgical periodontal treatment in patients with RA offers ...benefits in terms of the clinical activity and inflammatory markers of the disease.
A search was made of the Medline-PubMed, Cochrane, Embase and Scopus databases to identify studies on the relationship between the two disease processes, and especially on the effects of nonsurgical treatment in patients of this kind. The search was based on the following keywords: rheumatoid arthritis AND periodontitis (MeSH), rheumatoid arthritis AND periodontal treatment.
Eight articles on the nonsurgical treatment of patients with periodontitis and RA were finally included in the study. All of them evaluated clinical (DAS28) and laboratory test activity (ESR, CRP, IL-6, TNFα) before and after treatment. A clear decrease in DAS28 score and ESR was recorded, while other parameters such as CRP, IL-6 and TNFα showed a nonsignificant tendency to decrease as a result of treatment.
Nonsurgical treatment improved the periodontal condition of patients with periodontitis and RA, with beneficial effects upon the clinical and laboratory test parameters (DAS28 and ESR), while other inflammatory markers showed a marked tendency to decrease. However, all the studies included in the review involved small samples sizes and follow-up periods of no more than 6 months. Larger and particularly longitudinal studies are therefore needed to more firmly establish possible significant relations between the two disease processes.
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