Potential Effects of Essential Oil from Plinia cauliflora (Mart.) Kausel on Leishmania: In Vivo, In Vitro, and In Silico Approaches.

In the search for new chemotherapeutic alternatives for cutaneous leishmaniasis (CL), essential oils are promising due to their diverse biological potential. In this study, we aimed to investigate the chemical composition and leishmanicidal and anti-inflammatory potential of the essential oil isolated from the leaves of Plinia cauliflora (PCEO). The chemical composition of PCEO showed ß-cis-Caryophyllene (24.4%), epi-γ-Eudesmol (8%), 2-Naphthalenemethanol[decahydro-alpha] (8%), and trans-Calamenene (6.6%) as its major constituents. Our results showed that the PCEO has moderate cytotoxicity (CC50) of 137.4 and 143.7 µg/mL on mice peritoneal exudate cells (mPEC) and Vero cells, respectively. The PCEO was able to significantly decrease mPEC infection by Leishmania amazonensis and Leishmania braziliensis. The value of the inhibitory concentration (IC50) on amastigote forms was about 7.3 µg/mL (L. amazonensis) and 7.2 µg/mL (L. braziliensis). We showed that PCEO induced drastic ultrastructural changes in both species of Leishmania and had a high selectivity index (SI) > 18. The in silico ADMET analysis pointed out that PCEO can be used for the development of oral and/or topical formulation in the treatment of CL. In addition, we also demonstrated the in vivo anti-inflammatory effect, with a 95% reduction in paw edema and a decrease by at least 21.4% in migration immune cells in animals treated with 50 mg/kg of PCEO. Taken together, our results demonstrate that PCEO is a promising topical therapeutic agent against CL.

Evaluation of the Antioxidant Activity of Cis/Trans-N-Phenyl-1,4,4a,5,8,8a-Hexahydro-3,1-Benzoxazin-2-Imines.

The growing interest in the chemistry of unsaturated ring-fused 1,3-heterocycles, in this particular case 1,3-oxazines, arise in part from their versatile pharmacological applications. In the present article, the evaluation of the in vitro and ex vivo antioxidant activity of two cyclohexene-fused oxazines is discussed. The in vitro antioxidant activity was evaluated by trapping the ABTS and hydroxyl radicals as well as the inhibition of the enzyme acetyl-cholinesterase and hemolysis of erythrocytes by 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH). The results suggest that both unsaturated 1,3-oxazines are auspicious sources of biologically active compounds with good antioxidant properties. In addition, a comprehensive analysis of the interaction between these heterocycles with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals, as well as the measurements of redox potential, provided evidence for a mechanism of antioxidant activity that takes place through electron transfer (ET) processes.

Assessment of biosecurity practices and development of a scoring system in swine farms using item response theory.

Brazil is the fourth largest producer and exporter of pork in the world, but has never reported yet the occurrence of some economically important diseases such as porcine reproductive and respiratory syndrome (PRRS) and porcine epidemic diarrhea (PED). Most of the swine farms in Brazil are characterized by intensive production being part of large integrated companies, where biosecurity practices help to prevent the introduction and spread of disease-causing infectious agents. The assessment of biosecurity in farms is not straightforward because of the large number of practices that constitute an on-farm biosecurity program. It is therefore necessary to combine the measurement of several parameters in order to characterize the level of biosecurity on a given farm. Thus, the objective of the study was to develop a biosecurity score to estimate the biosecurity level (theta or θ) in swine farms using the item response theory (IRT) and explore the relationship between the scores and independent variables. The IRT is a latent trait method extensively used in other fields, and offers the advantage to quantify the latent trait, here the biosecurity level, and to identify the practices that discriminate the farms avoiding the use of extensive questionnaires and redundant questions. In this study, 604 farms were evaluated in the main swine production regions of the state of Rio Grande do Sul, Brazil. Thirty-five practices were considered in order to quantify the biosecurity level on a given farm. After a recursive process 14 practices were selected to compose the biosecurity score to estimate the biosecurity level (θ). The variables identified with greater capacity of distinguishing the farms as to their biosecurity level were if the farm has 'feed bin outside of the barn limit (external feed loading)', has 'perimetral fence around the farm or barn', and if 'transit of trucks inside the farm is prohibited'. The biosecurity level was associated with some independent variables, e.g. the farm operation type, the integrated company and some owner characteristics. In addition, the results demonstrated that biosecurity practices related to management (internal biosecurity) are adopted with higher frequency compared to segregation and sanitation practices (external biosecurity). The IRT model proved useful and valid to estimate the biosecurity level in swine farms. Moreover, the biosecurity score described here has a relatively low number of items, which makes the application of this tool easier and faster compared to other previously described biosecurity assessment.

Genetic diversity, virulence genotype and antimicrobial resistance of uropathogenic Escherichia coli (UPEC) isolated from sows.

BACKGROUND: Urinary tract infections (UTI) cause severe losses to the swine industry worldwide and uropathogenic Escherichia coli (UPEC) are the main agent isolated from UTI in sows. OBJECTIVE: The aim of this study was to investigate the virulence genes, assess the phylogenetic background, clonal diversity, and the pattern of resistance to antimicrobials in 186 isolates of UPEC isolated from sows in Brazil. MATERIALS AND METHODS: Urine samples from 300 sows of three herds with clinical signs from São Paulo State (Brazil) were screened for UTI; samples with suggestive results were submitted to bacterial isolation. E. coli strains isolated were characterized using disk diffusion technique, polymerase chain reaction and Single-enzyme amplification fragment length polymorphism (SE-AFLP). RESULTS: Virulence genes focH and papC were present in 78.5% and 58% of strains, respectively, followed by cnf1 (23.2%), afa (13.4%), sfa (11.3%), iucD (6.9%), and hlyA (1.6%). No clonal relatedness was found by SE-AFLP. A total of 98% of isolates (182/186) were multidrug resistant, and the highest levels of resistance were to sulfonamides, tetracycline, florfenicol, and ampicillin. Isolates were classified in phylogenetic group B1 (34.4%), followed by D (33.9%), E (30.1%) and A (1.6%). CONCLUSIONS: The data obtained suggest that pigs from clinically affected herds may serve as a reservoir of uropathogenic and multidrug-resistant E. coli strains.

Indigofera suffruticosa Mill. (Anil): Plant Profile, Phytochemistry, and Pharmacology Review.

Indigoferasuffruticosa Mill. (Fabaceae) is known as anil or anileira and also with other names, due to the production of a blue pigment, which is commonly used for yarn dyeing. It is distributed in some states of Brazil (Pernambuco, Paraíba, Mato Grosso, São Paulo, Bahia, Pará, and others) and is used in the popular medicine as a febrifuge, antispasmodic, diuretic, abortive, analgesic, purgative, or soothing agent against stomach and urinary problems, jaundice, and ulcers and also as an insecticide. In addition, I. suffruticosa can be used as animal feed. This review aimed at providing important data on the botanical, distribution, ethnopharmacology, phytochemical, pharmacological, and toxicity of I. suffruticosa based on the scientific literature. Information on I. suffruticosa was gathered via the Internet (from Elsevier, NCBI, and Sci-Hub) and libraries in the period from February to March 2016. More than 40 chemical compounds have been identified and a few compounds isolated, and the main origins are the essential oils, organic extracts, and aqueous extracts of different parts of the plant. I. suffruticosa and its active compounds possess wide pharmacological actions in the literature, such as anti-inflammatory, antibacterial, antifungal, antioxidative, antitumor, antimutagenic, anticonvulsant, gastroprotective, and hepatoprotective activities. Therefore, as an important traditional popular medicine, further studies on I. suffruticosa are required for the development of new drugs and therapeutics for various diseases.

Targeted therapies for the treatment of non-small-cell lung cancer: Monoclonal antibodies and biological inhibitors.

The usual treatments for patients with non-small-cell lung cancer (NSCLC), such as advanced lung adenocarcinoma, are unspecific and aggressive, and include lung resection, radiotherapy and chemotherapy. Recently, treatment with monoclonal antibodies and biological inhibitors has emerged as an effective alternative, generating effective results with few side effects. In recent years, several clinical trials using monoclonal antibodies presented potential benefits to NSCLC, and 4 of them are already approved for the treatment of NSCLC, such as cetuximab, bevacizumab, nivolumab and pembrolizumab. Also, biological inhibitors are attractive tolls for biological applications. Among the approved inhibitors are crizotinib, erlotinib, afatinib and gefitinib, and side effects are usually mild to intense. Nevertheless, biological molecule treatments are under development, and several new monoclonal antibodies and biological inhibitors are in trial to treat NSCLC. Also under trial study are as follows: anti-epidermal growth factor receptor (EGFR) antibodies (nimotuzumab and ficlatuzumab), anti-IGF 1 receptor (IGF-1R) monoclonal antibody (figitumumab), anti-NR-LU-10 monoclonal antibody (nofetumomab) as well as antibodies directly affecting the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) molecule (ipilimumab and tremelimumab), to receptor activator of nuclear factor-kappa B ligand (RANKL) (denosumab) or to polymerase enzyme (veliparib and olaparib). Among new inhibitors under investigation are poly-ADP ribose polymerase (PARP) inhibitors (veliparib and olaparib) and phosphatidylinositol 3-kinase (PI3K) inhibitor (buparlisib). However, the success of immunotherapies still requires extensive research and additional controlled trials to evaluate the long-term benefits and side effects.

Suppurative peritonitis by Klebsiella pneumoniae in captive gold-handed tamarin (Saguinus midas midas).

This report describes an outbreak of suppurative peritonitis caused by Klebsiella pneumoniae in an adult female of captive golden-handed tamarin (Saguinus midas midas). Two virulent and multidrug-resistant strains were isolated and classified through MLST as ST60 and ST1263. The microbiological diagnosis works as a support tool for preventive measures.

Antimicrobial resistance in Gram-negative bacilli isolated from infant formulas.

A total of 90 samples of infant formula (IF) were collected from the lactary of a teaching hospital, during a 4-month period from July to August 1999. The sanitary conditions of the formulas were analyzed, and a physiological characterization of Gram-negative bacillus isolates and antimicrobial susceptibility testing were performed. Colony counts were considered to be unacceptable for the majority of the IF samples and the contamination rates were related to inadequate handling. Coliforms (35 degrees C and 45 degrees C growth) were detected in most of the IF tested. Klebsiella pneumoniae, Citrobacter freundii, Cedacea davisae, Klebsiella planticola and Enterobacter cloacae were the isolates most commonly identified. Antimicrobial susceptibility testing showed significant resistance rates, particularly to amoxicillin/clavulanic acid, cefoxitin, cephalotin or ampicillin. One extended-spectrum beta-lactamase-producing K. pneumoniae strain was also recovered.