Molecular hybridization: A useful tool in the design of new drug prototypes

Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hyrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can results in compounds presenting modified selectivity profile, different and/or dual modes of action and reduced undesired side effects. So, in this described several example of different strategies for drug design, discovery and pharmacomodulation focused on new innovative hybrid compounds presenting analgesic, anti-inflammatory, platelet anti-aggregating, anti-infections, anticancer, cardio- and neuroactive properties.

Comparison of the biological behavior of wollastonite bioceramics prepared from synthetic and natural precursors

Wollastonite bioceramics prepared from synthetic and natural precursors were implanted in rats in bone and subcutaneous tissues. The implant sites were excised after 7, 30 and 120 days, fixed, dehydrated, embedded in paraffin wax for serial cutting and examined under transmitted light microscope. It was found a very similar behavior for both wollastonite bioceramics. They were biocompatible, bioactive and biodegradable when implanted in rat bone. The synthetic ceramic was more reabsorbable than the one from natural powder. When implanted in subcutaneous rat tissue, both materials elicited a mild initial inflammatory reaction that practically disappeared after 120 days. Both materials were encapsulated with a very thin fibrous capsule and slightly reabsorbed at their surfaces. None of the materials induced ectopic osteogenesis. According to the results, the studied materials seem to be able for manufacturing reabsorbable bone implants.

Biological response to wollastonite doped α-tricalcium phosphate implants in hard and soft tissues in rats

The biological response following subcutaneous and bone implantation of β-wollastonite(β-W)-doped α-tricalcium phosphate bioceramics in rats was evaluated. Tested materials were: tricalcium phosphate (TCP), consisting of a mixture of α- and β-polymorphs; TCP doped with 5 wt. % of β-W (TCP5W), composed of α-TCP as only crystalline phase; and TCP doped with 15 wt. % of β-W (TCP 15), containing crystalline α-TCP and β-W. Cylinders of 2×1 mm were implanted in tibiae and backs of adult male Rattus norvegicus, Holtzman rats. After 7, 30 and 120 days, animals were sacrificed and the tissue blocks containing the implants were excised, fixed and processed for histological examination. TCP, TCP5W and TCP15W implants were biocompatible but neither bioactive nor biodegradable in rat subcutaneous tissue. They were not osteoinductive in connective tissue either. However, in rat bone tissue β-W-doped α-TCP implants (TCP5W and TCP 15W) were bioactive, biodegradable and osteoconductive. The rates of biodegradation and new bone formation observed for TCP5W and TCP15W implants in rat bone tissue were greater than for non-doped TCP.

Identificação de diterpenos clerodânicos em diferentes órgãos de Casearia sylvestris Swartz

Casearia sylvestris Swartz (Salicaceae) is a tree or shrub distributed widely in Brazil, where it is used in popular medicine. Several bioactive clerodane diterpenes typical of Casearia have been isolated from this species (e.g. casearins and casearvestrins). The main objective of this study was to identify clerodane diterpenes in various organs of C. sylvestris, using chromatographic and spectroscopic analytical techniques. The extracts of the different plant parts were analyzed by thin layer chromatography, high performance liquid chromatography with diode array detector and 1H nuclear magnetic resonance. In the chromatographic analysis, clerodane diterpenes isolated from C. sylvestris were used as standards, including rel-19Sacetóxi-18R- butanoilóxi-18,19- epóxi -6S -hidróxi -2R-(2-metilbutanoilóxi) -5S, 8R, 9R, 10S -cleroda-3,13(16),14-triene, isolated for the first time from the stems. Phytochemical profiles of the organs were produced, which indicated the presence of clerodane diterpenes in all parts of the plant, notably in the leaves. The results also suggest that the main clerodane diterpenes in the stems, flowers and roots had conjugated double-bond patterns that differed from those found in the leaves.

Evaluation of blood compatibility of plasma deposited heparin-like films and SF6 plasma treated surfaces

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A human retrieval study of plasma-sprayed hydroxyapatite-coated plateau root form implants after 2 months to 13 years in function

Calcium phosphate-based bioactive ceramics in various physical and chemical formulations have been extensively utilized as biomaterials for bone regeneration/conduction. However, the determination of their in vivo temporal behavior from the short to long term in humans has been a challenge due to the lack of physical reference for morphologic and morphometric evaluation. The present study evaluated bone morphology and morphometry (bone-to-implant contact [BIC]) around plasma-sprayed hydroxyapatite (PSHA)-coated endosseous implants that were retrieved due to prosthetic reasons while successfully in function at the posterior region of the jaws from as early as 2 months to ~13 years after a 6-month healing period after placement. Bone morphology was evaluated by light microscopy, and BIC was determined using computer software. Irrespective of the time in vivo, lamellar bone was observed in close contact with the implant PSHA-coated surface and between plateaus. BIC ranged from ~35-95%, was highly directional, and Haversian-like osteonic morphology between plateaus was observed for most implants. The PSHA coating was present with little variation in thickness between the samples retrieved regardless of time in vivo. © 2010 by Begell House, Inc.

Carotenoides em abóboras

The present literature review highlights the importance of carotenoids as bioactive compound, and its potential application in functional foods. It were detailed the origin, chemical characteristics and sources of the carotenoids. It were also studied the most used methods to quantify and qualify the carotenoids, including spectrophotometry, mass spectrometry, high-performance liquid chromatography, gas chromatography and colorimetry. The pumpkin intake is recommended because they represent important source of carotenoids such as α-carotene, β-carotene and lutein.

Evaluating of the activity antioxidant and fatty acids profile of lychee seeds (Litchi chinensis SONN.)

Purpose: The purpose of this paper is to characterize lychee seeds regarding their centesimal composition, and also to evaluate their antioxidant potential and fatty acid profile. Design/methodology/approach: To obtain the extract, dehydrated and grinded seeds were extracted with ethyl alcohol for 30 min, at a proportion of 1:3 of seeds:ethyl alcohol, under continuous agitation, at room temperature. Afterwards, the mixture was filtered and the supernatant subjected to a rotoevaporator at 40oC aiming to determine, by direct weighing, the extract dry matter yield. Findings: The largest found values went to the total carbohydrates (72.75 percent). In the oil from the lychee seeds there was a high percentage of unsaturated fatty acids, the main component being linoleic, considered an essential fatty acid. Research limitations/implications: Implies the identification of compounds biativos extracted from seeds of tropical and subtropical fruits, and to prevent certain types of diseases. Originality/value: The article tries to identify new source of phenolic compounds extracted from fruit. © Emerald Group Publishing Limited.

Antioxidant capacity and total phenolic content of hydrothermally-treated 'Fuerte' avocado

Avocados possess high nutritional value with proven effectiveness in preventing cardiovascular diseases, attributed primarily to their unsaturated fatty acids content. This fruit is also rich in carotenoids and vitamins, particularly vitamin E. This work evaluates the antioxidant capacity and total phenolic content of hydrothermally-treated Fuerte avocado. Fruits were selected and hydrothermally treated at 45°C for 5, 10, 15 and 20 min. They were then stored in a refrigerator (10 ± 10°C and 90±5% relative humidity) and evaluated over a 15-day period. The total phenolic content increased up to the sixth day of storage, and decreased thereafter, without differences between the treatments. The percentage of antioxidant capacity of the control and the hydrothermally-treated samples for 5 and 10 min increased during storage. Untreated fruits showed the highest percentage of antioxidant capacity. However, the antioxidant capacity of avocado fruits subjected to these treatments declined starting on the twelfth day of storage, possibly due to the fruits' senescence. Hydrothermal treatments for 15 and 20 min delayed fruit senescence while the antioxidant capacity continued to increase up to the fifteenth day of storage. No significant correlation was found between antioxidant capacity and total phenolic content. The antioxidant capacity of ripe Fuerte avocado was higher than that of unripe or overripe avocado.

Biocompatibility analysis of Bioglass® 45S5 and Biosilicate® implants in the rabbit eviscerated socket

Purpose: Bioactive glass and bioactive glass-ceramic cone implants were placed in the rabbit eviscerated socket to assess their biocompatibility. Methods: Fifty-one Norfolk albino rabbits underwent evisceration of the right eye followed by implantation of cones made from Bioglass® 45S5 (control group) and two types of bioactive glass-ceramic (Biosilicate®), a single- and a two-phase bioactive glass-ceramic implants into the scleral cavity. Postoperative reactions, animal behavior and socket conditions were monitored daily. Clinical exam, biochemical evaluations, and orbit computed tomographic scan were done at 7, 90, and 180 days post-procedure. After that, the animals were euthanized, and the orbital content was removed and prepared to light microscopy with morphometric evaluation and scanning electron microscopy examination. Statistical analysis was done by parametric and non-parametric analysis of variance, complemented by Dunn's and Tukey's tests (p<0.05). Results: All animals did not develop systemic toxicity throughout the experimental period and also did not have orbit infection, implant migration or extrusion. Morphological analysis demonstrated pseudocapsule around all implants. Bioglass® and single-phase Biosilicate® implants induced less inflammation and pseudocapsule formation than two-phase Biosilicate® cones. Seven days post-procedure, the inflammatory reaction was intense and gradually decreased throughout the experiment. Tissue reaction was least intense in animals receiving Bioglass® implants. Conclusions: We observe discrete differences among the studied materials, with best responses obtained with use of Bioglass® 45S5 and single-phase Biosilicate®. The authors agree these implants might be useful in the management of the anophthalmic socket. © 2012 Informa Healthcare USA, Inc.

The challenges of treating a fused tooth

This paper describes and discusses the multidisciplinary treatment involving a permanent maxillary lateral incisor fused to a supernumerary tooth, both presenting pulp necrosis and periapical lesion. A 15-year-old male patient sought treatment complaining of pain, swelling and mobility on the maxillary right lateral incisor. After clinical and radiographic examination, root canal preparation was performed according to the crown-down technique and a calcium hydroxide dressing was placed for 15 days. The patient returned and the definitive endodontic filling was done with thermomechanical compaction of gutta-percha and sealer. After 18 months, clinical and radiographic examinations were carried out and no pain or swelling was reported. Two years after endodontic treatment, the patient returned for periodontal and cosmetic treatments. Nine months later, a cone-beam computed tomography (CBCT) revealed that the previously detected periodontal defect and periapical lesion were persistent. Apical endodontic surgery was indicated. The supernumerary tooth was removed, the communicating distal surface was filled and the surgical site received bioactive glass and demineralized bovine organic bone. The pathological tissue was submitted to histopathological examination and the diagnosis was periapical cyst. One year after the apical endodontic surgery, CBCT showed bone formation at maxillary lateral incisor apical area. Two years after the surgery, the restoration was replaced due to aesthetic reasons and periapical radiograph showed success after 5 years of treatment. A correct diagnosis and establishment of an adequate treatment plan resulted in a successful management of the case.

Soursop (Annona muricata L.) and sugar apple (Annona squamosa L.): Antioxidant activity, fatty acids profile and determination of tocopherols

Purpose: This study aims to analyze the soursop and sugar apple seeds as to its composition, to evaluate the antioxidant potential of seeds extract and characterize the oil extracted from them, regarding the fatty acids profile and content of tocopherols. Design/methodology/approach: To obtain the extracts, dried and crushed seeds were extracted with ethanol for 30 minutes, at a ratio of 1:3 (m/m, seed: ethyl alcohol) under continuous stirring at room temperature. Then, the mixture was filtered and the supernatants subjected to rotoevaporator at 40°C aiming to determine, by direct weighing, the yields of dry extracts. Findings: According to the results, the soursop and sugar apple seeds constituted significant sources of lipids, proteins and carbohydrates and can therefore be used in food and feed, and offer relevant antioxidant activity of phenolic compounds. The oil seeds are a good source of unsaturated fatty acids, especially oleic and linoleic acids and they have significant amounts of total tocopherol. Research limitations/implications: Implications are the identification of bioactive compounds extracted from seeds of tropical and subtropical fruits, and to prevent certain types of diseases. Practical implications: The information presented might be directly used for developing of functional foods such as fruits. Originality/value: The article tries to identify new source of compounds extracted from fruits. © Emerald Group Publishing Limited.

Annona sp: Plants with multiple applications as alternative medicine - a review

Annona species have been used as a natural remedy for a variety of illnesses with antiparasitic, antispasmodic, antidiarrheal, antiulcer, sedative, analgesic, hypotensive, and vermifugal effects. These properties are due to the presence of a number of bioactive compounds on the leaves, fruit, seeds, and stem. The aim of this review is to show the main species of Annona, their medicinal properties and the chemical constituents that may be related to these effects. In the leaves it is possible to find acetogenins, annopentocins A, B, and C, cis- and trans-annomuricin-D-ones, goniothalamicin, arianacin, and javoricin, related to anticancer properties. Quercetin-3-O-glucoside, also found in the leaves mediates antidiabetic and antioxidative effects. In the fruit are found annonaine, nornuciferine and asimilobine, associated to antidepressive effects. In the seeds are found muricatetrocin A and muricatetrocin B, longifolicin, corossolin, corossolone, uvarigrandin A, bullatacin, squamotatin. These acetogenins are associated with anticancer effects. Cyclosquamosin B, quercetin, and cyclosquamosin from the seeds have respectively vasorelaxant, antithyroidal and, antiinflammatory activity. In the stem parts there are several components as N-trans-feruloyltyramine, N-p-coumaroyltyramine, and N-trans-caffeoyltyramine, lignans, syringaresinol, syringaldehyde, beta-sitosterol and beta-sitosterol-beta-D-glucoside which exhibit antiplatelet aggregation activity. Copaene, patchoulane, 1H-cycloprop (e) azulene and kaur-16-en-19-oic acid found in the barks exhibit significant central as well as peripheral analgesic and antiinflammatory activities. The properties of the biological compounds in Annona species support information that may provide validation for its medicinal uses, but further studies should be performed to establish ideal and safe doses of consumption to ensure the effectiveness of the benefits. © 2012 Bentham Science Publishers.

Dispersed hydroxyapatite bioglass 45S5 composites: Comparative evaluation of the use of bovine bone and synthetic hydroxyapatite

The bovine bone and sintetic hydroxyapatite (HA) bioceramics are reference materials to employment as a bone substitute, however, their slow rate of degradation and its low rate of bioactivity index (Ib) are presented as limiting factors for application as bone graft. In contrast, the bioglass is a resorbable and osteoinductive material. the present work objective the development of composites of dispersed bovine bone or sintetic HA in silicate-phosphate bioglass, seeking to obtain a biomaterial with properties suitable for application as bone grafts. The composites were prepared by mixing between the powder components followed by sintering for 1h. Were used HA and bioglass (45S5) with particle size <240μm. The tested proportions of HA/45S5 were 20/80, 30/70 and 40/60 (wt%). The composites characterization was made employing scanning electron microscopy, Infra-Red Spectrometry and hydrolytic resistance test. The test results indicate the potential use of the materials developed for applications such as bone graft. © (2012) Trans Tech Publications, Switzerland.

C-terminal processing of the teneurin proteins: Independent actions of a teneurin C-terminal associated peptide in hippocampal cells

Many neuropsychiatric conditions have a common set of neurological substrates associated with the integration of sensorimotor processing. The teneurins are a recently described family of proteins that play a significant role in visual and auditory development. Encoded on the terminal exon of the teneurin genes is a family of bioactive peptides, termed teneurin C-terminal associated peptides (TCAP), which regulate mood-disorder associated behaviors. Thus, the teneurin-TCAP system could represent a novel neurological system underlying the origins of a number of complex neuropsychiatric conditions. However, it is not known if TCAP-1 exerts its effects as part of a direct teneurin function, whereby TCAP represents a functional region of the larger teneurin protein, or if it has an independent role, either as a splice variant or post-translational proteolytic cleavage product of teneurin. In this study, we show that TCAP-1 can be transcribed as a smaller mRNA transcript. After translation, further processing yields a smaller 15. kDa protein containing the TCAP-1 region. In the mouse hippocampus, immunoreactive (ir) TCAP-1 is exclusively localized to the pyramidal layers of the CA1, CA2 and CA3 regions. Although the localization of TCAP and teneurin in hippocampal regions is similar, they are distinct within the cell as most ir-teneurin is found at the plasma membrane, whereas ir-TCAP-1 is predominantly found in the cytosol. Moreover, in mouse embryonic hippocampal cell culture, FITC-labeled TCAP-1 binds to the plasma membrane and is taken up into the cytosol via dynamin-dependent caveolae-mediated endocytosis. Our data provides novel evidence that TCAP-1 is structurally and functionally distinct from the larger teneurins. © 2012.