Genetic evaluation and activity of antifungal against clinical isolate Candida albicans biofilms

Candida yeasts are common in the oral cavity and can cause candidosis in the presence of predisposing factors, especially diabetes. The manifestation of the disease is related to this set of local factors such as the presence of dental prostheses, salivary pH, salivary flow and tobacco and the ability to form biofilms. Biofilms are specific and organized communities of cells under the control of signaling molecules rather than random accumulations of cells resulting from cell division and frequently are drugs resistance. Aim: The objectives of this study were to determine the genetic patterns of these C. albicans isolates and to evaluate the in vitro activity amphotericin B and caspofungin against C. albicans biofilms. Methods: Microbial samples were collected from subgingival sites and seeded in CHROMagar for subsequent identification of C. albicans by PCR. Genotypes were defined based on the identification of the transposable introns in the 25S rDNA by PCR. Results: In this study, 6 strains were identified as C. albicans and of these, 3 strains were genotype A and 3 were genotype B. The results showed that both amphotericin B and caspofungin exhibited strong antifungal activities against C. albicans biofilm formation and inhibiting the biofilm formation ranging from 70.8 – 95.3% and 77.7 - 88.7%, respectively. The antifungals studied had low inhibitory effect on preformed biofims, ranging from 39.5 - 50.8% for amphotericin B and from 23.1 - 36.9% for caspofungin at the same concentration. The activity of the two drugs was most effective in inhibit biofilm formation.

Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containing an N-Acyl hydrazone subunit

A series of anti-inflammatory derivatives containing an N-acyl hydrazone subunit (4a–e) were synthesized and characterized. Docking studies were performed that suggest that compounds 4a–e bind to cyclooxygenase (COX)-1 and COX-2 isoforms, but with higher affinity for COX-2. The compounds display similar anti-inflammatory activities in vivo, although compound 4c is the most effective compound for inhibiting rat paw edema, with a reduction in the extent of inflammation of 35.9% and 52.8% at 2 and 4 h, respectively. The anti-inflammatory activity of N-acyl hydrazone derivatives was inferior to their respective parent drugs, except for compound 4c after 5 h. Ulcerogenic studies revealed that compounds 4a–e are less gastrotoxic than the respective parent drug. Compounds 4b–e demonstrated mucosal damage comparable to celecoxib. The in vivo analgesic activities of the compounds are higher than the respective parent drug for compounds 4a–b and 4d–e. Compound 4a was more active than dipyrone in reducing acetic-acid-induced abdominal constrictions. Our results indicate that compounds 4a–e are anti-inflammatory and analgesic compounds with reduced gastrotoxicity compared to their respective parent non-steroidal anti-inflammatory drugs.

Evaluation and degradation chemistry of orbifloxacin using LC-MS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Are the preference and selection patterns of hermit crabs for gastropod shells species- or site-specific?

Experimental analyses of hermit crabs and their preferences for shells are essential to understand the intrinsic relationship of the crabs` dependence on shells, and may be useful to explain their shell use pattern in nature. The aim of this study was to evaluate the effect of crab species and site on the pattern of shell use, selection, and preference in the south-western Atlantic hermit crabs Pagurus brevidactylus and Pagurus criniticornis, comparing sympatric and allopatric populations. Differently from the traditional approach to evaluate shell preference by simply determining the shell selection pattern (i.e., the number of shells of each type selected), preference was defined (according to [Liszka, D., Underwood, AJ., 1990. An experimental design to determine preferences for gastropod shells by a hermit-crab. J. Exp. Mar. Biol. Ecol., 137(1), 47-62]) by the comparison of the number of crabs changing for a particular shell type when three options were given (Cerithium atratum, Morula nodulosa, and Tegula viridula) with the number of crabs changing for this same type when only this type was offered. The effect of crab species was tested at Cabelo Gordo Beach, where P. brevidacrylus was found occupying shells of C. atratum, M. nodulosa, and T viridula in similar frequencies, whereas P. criniticornis occupied predominantly shells of C atratum. In laboratory experiments the selection patterns of the two hermit-crab species for these three gastropods were different, with P criniticornis selecting mainly shells of C atratum, and R brevidactylus selecting more shells of M. nodulosa. The shell preference was also dependent on crab species, with P. criniticornis showing a clear preference for shells of C atratum, whereas P. brevidactylus did not show a preference for any of the tested shells. The effect of site was tested for the two species comparing data from Cabelo Gordo to Preta (P brevidactylus) and Araca beaches (P. criniticornis). The pattern of shell use, selection, and preference was demonstrated to be dependent on site only for P. brevidactylus. The results also showed that the shell use pattern of P criniticornis can be explained by its preference at both sites, whereas for P. brevidactylus it occurred only at Cabelo Gordo, where the absence of preference was correlated with the similar use of the three gastropod species studied. Finally, the results showed that the shell selection pattern cannot be considered as a measure of shell preference, since it overestimates crab selectivity. (C) 2009 Elsevier B.V. All rights reserved.

Chemical evaluation and thermal behavior of Brazil nut oil obtained by different extraction processes

Brazil nut richness has been widely studied aiming at finding transformation models that increase its yield, keep its quality, reduce costs, and increase its productivity. The objective of this study is to evaluate the spectroscopic profile and the chemical and thermal behavior of Brazil nut oil obtained by different extraction processes. Lipid soxhlet extractions with petroleum ether and hexane, and using hydraulic pressing and supercritical carbon dioxide (CO2) were performed. The physicochemical analyses showed an acidity index with significant differences between the samples obtained by hydraulic pressing and supercritical CO2. The peroxide index presented significant difference for the oil obtained by hydraulic pressing compared to that obtained by the other extraction processes. The fatty acid profiles showed a relevant presence of the omega series (w-3, w-6, and w-9) with significant differences for the extraction processes evaluated. The results of the thermogravimetric and differential analyses did not indicate changes in mass loss and presented predominantly exothermic behavior. The spectroscopic profiles indicate that the extraction processes do not change the spectral profile of the oils. (c) 2011 Elsevier Ltd. All rights reserved.

DETERMINATION OF DICLOFENAC SODIUM IN RABBIT PLASMA BY HPLC/UV: EVALUATION AND CHARACTERIZATION OF ITS CRYSTALLINE FORMS, ANHYDROUS AND HYDRATE, ON THE ANTIPYRETIC EFFECT

Diclofenac sodium (DS) is a non-steroidal anti-inflammatory drug that is widely prescribed for the treatment of rheumatoid arthritis and post-surgery analgesia. The active pharmaceutical ingredient is the anhydrous form; however, it can also exist in hydrate form. In this context, knowing the properties of the solid state is important and relevant in the pharmaceutical area because they have a significant impact on the solubility, bioavailability, and chemical stability of the drugs. In the present study, data from XRPD, FTIR spectroscopy, and thermal analysis were used for the identification and characterization of DS forms (anhydrous and hydrate). An HPLC method was optimized to evaluate the plasma concentration of DS in rabbits. The optimized method exhibited good linearity over the range 0.1-60 mu g/mL with correlation coefficients of >0.9991. The mean recovery was 100%. Precision and accuracy were determined within acceptable limits. Finally, to compare the pharmacological properties of anhydrous and hydrate DS forms, we investigated their effects in the febrile response induced by lipopolysaccharide from E. coli in rabbits. The results show that the antipyretic effect of anhydrous and hydrate DS forms are similar.

Synthesis, Biological Evaluation, And Molecular Modeling of Chalcone Derivatives As Potent Inhibitors of Mycobacterium tuberculosis Protein Tyrosine Phosphatases (PtpA and PtpB)

Tuberculosis (TB) is a major infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the World Health Organization (WHO), about 1.8 million people die from TB and 10 million new cases are recorded each year. Recently, a new series of naphthylchalcones has been identified as inhibitors of Mtb protein tyrosine phosphatases (PTPs). In this work, 100 chalcones were designed, synthesized, and investigated for their inhibitory properties against MtbPtps. Structure-activity relationships (SAR) were developed, leading to the discovery of new potent inhibitors with IC50 values in the low-micromolar range. Kinetic studies revealed competitive inhibition and high selectivity toward the Mtb enzymes. Molecular modeling investigations were carried out with the aim of revealing the most relevant structural requirements underlying the binding affinity and selectivity of this series of inhibitors as potential anti-TB drugs.

Histopathological evaluation and risk factors related to the development of pouchitis in patients with ileal pouches for ulcerative colitis

OBJECTIVE: Many changes in mucosal morphology are observed following ileal pouch construction, including colonic metaplasia and dysplasia. Additionally, one rare but potential complication is the development of adenocarcinoma of the reservoir. The aim of this study was to evaluate the most frequently observed histopathological changes in ileal pouches and to correlate these changes with potential risk factors for complications. METHODS: A total of 41 patients were enrolled in the study and divided into the following three groups: a non-pouchitis group (group 1) (n = 20; 8 males; mean age: 47.5 years) demonstrating optimal outcome; a pouchitis without antibiotics group (group 2) (n = 14; 4 males; mean age: 47 years), containing individuals with pouchitis who did not receive treatment with antibiotics; and a pouchitis plus antibiotics group (group 3) (n = 7; 3 males; mean age: 41 years), containing those patients with pouchitis who were administered antibiotics. Ileal pouch endoscopy was performed, and tissue biopsy samples were collected for histopathological analysis. RESULTS: Colonic metaplasia was found in 15 (36.6%) of the 41 patients evaluated; of these, five (25%) were from group 1, eight (57.1%) were from group 2, and two (28.6%) were from group 3. However, no correlation was established between the presence of metaplasia and pouchitis (p = 0.17). and no differences in mucosal atrophy or the degree of chronic or acute inflammation were observed between groups 1, 2, and 3 (p > 0.45). Moreover, no dysplasia or neoplastic changes were detected. However, the degree of mucosal atrophy correlated well with the time of postoperative follow-up (p = 0.05). CONCLUSIONS: The degree of mucosal atrophy, the presence of colonic metaplasia, and the degree of acute or chronic inflammation do not appear to constitute risk factors for the development of pouchitis. Moreover, we observed that longer postoperative follow-up times were associated with greater degrees of mucosal atrophy.

Synthesis, biological evaluation and molecular docking studies of 3-(triazolyl)coumarin derivatives: Effect on inducible nitric oxide synthase

A series of 3-(triazolyl)-coumarins were synthesized and tested as anti-inflammatory agents. It was possible to infer that these compounds do not alter the interaction of LPS with TLR-4 or TLR-2, as the intracellular pathways involved in the TNF-alpha secretion and COX-2 activity were not affected. Nevertheless, the compounds inhibited iNOS-derived NO production, without affecting the eNOS activity. The outcome of the docking studies showed that it pi center dot center dot center dot pi interactions with the heme group are important for the iNOS inhibition, thus making compound 3c a promising lead. Moreover, the efficacy of this compound was visualized by the reduced number of neutrophils in the LPS-inflamed subcutaneous tissue. Together, biological and docking data show that triazolyl-substituted coumarins, that can act on iNOS, are a good scaffold to be explored. (C) 2012 Elsevier Masson SAS. All rights reserved.

From inverted pendulum to N-link chain: inertial sensors-based assessment of movement kinematics and dynamics for functional evaluation and rehabilitation

Despite several clinical tests that have been developed to qualitatively describe complex motor tasks by functional testing, these methods often depend on clinicians' interpretation, experience and training, which make the assessment results inconsistent, without the precision required to objectively assess the effect of the rehabilitative intervention. A more detailed characterization is required to fully capture the various aspects of motor control and performance during complex movements of lower and upper limbs. The need for cost-effective and clinically applicable instrumented tests would enable quantitative assessment of performance on a subject-specific basis, overcoming the limitations due to the lack of objectiveness related to individual judgment, and possibly disclosing subtle alterations that are not clearly visible to the observer. Postural motion measurements at additional locations, such as lower and upper limbs and trunk, may be necessary in order to obtain information about the inter-segmental coordination during different functional tests involved in clinical practice. With these considerations in mind, this Thesis aims: i) to suggest a novel quantitative assessment tool for the kinematics and dynamics evaluation of a multi-link kinematic chain during several functional motor tasks (i.e. squat, sit-to-stand, postural sway), using one single-axis accelerometer per segment, ii) to present a novel quantitative technique for the upper limb joint kinematics estimation, considering a 3-link kinematic chain during the Fugl-Meyer Motor Assessment and using one inertial measurement unit per segment. The suggested methods could have several positive feedbacks from clinical practice. The use of objective biomechanical measurements, provided by inertial sensor-based technique, may help clinicians to: i) objectively track changes in motor ability, ii) provide timely feedback about the effectiveness of administered rehabilitation interventions, iii) enable intervention strategies to be modified or changed if found to be ineffective, and iv) speed up the experimental sessions when several subjects are asked to perform different functional tests.

Scalable and Seamless Discovery and Selection of Services in Mobile Cloud Computing

Mobile devices are now capable of supporting a wide range of applications, many of which demand an ever increasing computational power. To this end, mobile cloud computing (MCC) has been proposed to address the limited computation power, memory, storage, and energy of such devices. An important challenge in MCC is to guarantee seamless discovery of services. To this end, this thesis proposes an architecture that provides user-transparent and low-latency service discovery, as well as automated service selection. Experimental results on a real cloud computing testbed demonstrated that the proposed work outperforms state of-the-art approaches by achieving extremely low discovery delay.