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A new 5-O-β-D-glucopyranosyl-4-(4-hydroxyphenyl)-7-methoxy-2H-chromen-2-one (1), together with four known compounds, one coumarin, 5-O-β-D-galactopyranosyl-4-(4-hydroxyphenyl)-7-methoxy-2H-chromen-2-one (2) and three cucurbitacins, 23,24-dihydrocucurbitacin F (3), 23,24-dihydro-25-acetylcucurbitacin F (4) and 2-O-β-D-glucopyranosyl-23,24-dihydrocucurbitacin F (5) have been isolated and characterised from the ethanol extract of Coutarea hexandra fruits. Their structures have been established by spectroscopic analysis (NMR and MS). Interpretation of the HMQC, HMBC, COSY-45 and NOESY experiments permitted us to establish stereochemistry of the natural products. All compounds were tested in cytotoxicity assays against the breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines. [ABSTRACT FROM AUTHOR]

Despite its importance in pathogenesis, the hematogenous dissemination pathway of Borrelia burgdorferi is still largely uncharacterized. To probe the molecular details of transendothelial migration more easily, we studied this process using cultured primary or telomerase-immortalized human microvascular endothelial cells in a medium that maintains both the human cells and the spirochetes. In B. burgdorferi -infected monolayers, we observed ~55% of wild-type spirochetes crossing the monolayer. Microscopic characterization revealed entrance points across the cellular surface rather than at cellular junctions, supporting a transcellular route. In support of this pathway, locking the endothelial junctions using a vascular endothelial protein tyrosine phosphatase (VE-PTP) inhibitor did not reduce transendothelial migration. We also used inhibitors to block the most common endocytic pathways to elucidate effectors that might be involved in B. burgdorferi uptake and/or transmigration. Directly inhibiting Cdc42 reduced spirochete transmigration by impeding internalization. However, blocking Rac1 alone dramatically reduced transmigration by ~84% and resulted in a concomitant doubling in spirochete accumulation in the cell. Our combined results support that B. burgdorferi internalization is an intermediate step in the transendothelial migration process, which requires both Cdc42 and Rac1; Cdc42 is needed for spirochete internalization, while Rac1 is required for cellular egress. These are the first two host proteins implicated in B. burgdorferi transmigration across endothelial cells.IMPORTANCELyme borreliosis is caused by Borrelia burgdorferi and related bacteria. It is the most common tick-transmitted illness in the Northern Hemisphere. The ability of this pathogen to spread to a wide variety of locations results in a diverse set of clinical manifestations, yet little is known regarding vascular escape of the spirochete, an important pathway for dissemination. Our current work has studied the traversal of B. burgdorferi across a monolayer of microvascular endothelial cells grown using a new culture system. We show that this occurs by passage of the spirochetes directly through cells rather than at cellular junctions and that internalization of B. burgdorferi is an intermediate step in transmigration. We also identify the first two host proteins, Cdc42 and Rac1, that are used by the spirochetes to promote traversal of the cellular monolayer. Our new experimental system also provides a new avenue for further studies of this important process.

The goal of the current study was to identify ways to increase awareness and engagement in kitten fostering programs (KFPs) among residents of areas with a high intake of kittens to animal shelters in Southern California (i.e., Los Angeles County). Specifically, we aimed to understand residents': (1) awareness of KFPs and kitten overpopulation issues, (2) interest in fostering kittens with an animal welfare organization, (3) concerns about fostering, (4) perceived ability to meet common KFP requirements, and (5) perceptions of potential KFP marketing/messaging and communication methods. Participants included 283, predominantly Hispanic/Latinx adults aged 18 years or older who resided in Los Angeles County and who lived in one of 12 zip codes with a high rate of kitten shelter intake. Survey results indicated that more than one quarter of participants had engaged in fostering on their own without an animal shelter or rescue program. One-third of the total sample, and more than two-thirds of participants who had already fostered cats and kittens on their own, were open to fostering kittens in partnership with an animal shelter. A majority of individuals who were interested in fostering had not seen advertising for fostering programs; Spanish-language participants were significantly less likely than expected to have encountered program advertisements. The most prevalent concerns about fostering in our sample were centered on the time (79%), cost (78%), and space (77%) required to engage in fostering. Text, email, social media, and mail were among the most preferred methods for marketing and communication, with some variation between Spanish and English language respondents. Opportunities for increasing engagement included, but were not limited to, improving the promotion of program advertisements using animal-welfare and cost-focused messaging approaches and improving the dissemination and marketing of Spanish-language materials. Providing community members with realistic expectations of the time, resources, and support they will get from animal welfare organizations may improve engagement in KFPs, as well as identifying alternative resources and supports (e.g., transportation, in-home veterinary visits) to assist community members in serving animals in their community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 McDonald, Miller, Fried, Olmedo and Matijczak.)

Implant therapy using osseointegratable titanium (Ti) dental implants has revolutionized clinical dental practice and has shown a high rate of success. However, because a metallic implant is in contact with body tissues and fluids in vivo, ions/particles can be released into the biological milieu as a result of corrosion or biotribocorrosion. Ultrananocrystalline diamond (UNCD) coatings possess a synergistic combination of mechanical, tribological, and chemical properties, which makes UNCD highly biocompatible. In addition, because the UNCD coating is made of carbon (C), a component of human DNA, cells, and molecules, it is potentially a highly biocompatible coating for medical implant devices. The aim of the present research was to evaluate tissue response to UNCD-coated titanium micro-implants using a murine model designed to evaluate biocompatibility. Non-coated (n = 10) and UNCD-coated (n = 10) orthodontic Ti micro-implants were placed in the hematopoietic bone marrow of the tibia of male Wistar rats. The animals were euthanized 30 days post implantation. The tibiae were resected, and ground histologic sections were obtained and stained with toluidine blue. Histologically, both groups showed lamellar bone tissue in contact with the implants (osseointegration). No inflammatory or multinucleated giant cells were observed. Histomorphometric evaluation showed no statistically significant differences in the percentage of BIC between groups (C: 53.40 ± 13% vs. UNCD: 58.82 ± 9%, p > 0.05). UNCD showed good biocompatibility properties. Although the percentage of BIC (osseointegration) was similar in UNCD-coated and control Ti micro-implants, the documented tribological properties of UNCD make it a superior implant coating material. Given the current surge in the use of nano-coatings, nanofilms, and nanostructured surfaces to enhance the biocompatibility of biomedical implants, the results of the present study contribute valuable data for the manufacture of UNCD coatings as a new generation of superior dental implants.

Bone is a hierarchical material that has inspired the design of biopolymer-derived biocomposites for tissue engineering purposes. The present study sought to synthesize and perform the physicochemical characterization and biocompatibility of a collagen-silica-based biocomposite for potential application in bone tissue engineering. Ultrastructure, biodegradability, swelling behavior, and biocompatibility properties were analyzed to gain insight into the advantages and limitations to the use of this biomaterial as a bone substitute. Scanning electron microscopy analysis showed a packed-collagen fibril matrix and silica particles in the biocomposite three-dimensional structure. As shown by analysis of in vitro swelling behavior and biodegradability, it would seem that the material swelled soon after implantation and then suffered degradation. Biocompatibility properties were analyzed in vivo 14-days postimplantation using an experimental model in Wistar rats. The biocomposite was placed inside the hematopoietic bone marrow compartment of both tibiae (n = 16). Newly formed woven bone was observed in response to both materials. Unlike the pure-collagen-tissue interface, extensive areas of osseointegration were observed at the biocomposite-tissue interface, which would indicate that silica particles stimulated new bone formation. Agglomerates of finely particulate material with no inflammatory infiltrate or multinucleated giant cells were observed in the bone marrow implanted with the biocomposite. The biocomposite showed good biocompatibility properties. Further studies are necessary to evaluate their biological behavior over time., (© 2021 Wiley Periodicals LLC.)

The occurrence of multidrug-resistant pathogens in the food chain causes health problems in humans, thus, research for novel antimicrobials to combat their growth is of interest. This study evaluates the antimicrobial potential of several combinations of peptide-protein extracts (PCs) consisting of peptide extracts from three native probiotic strains, Lactiplantibacillus plantarum UTNGt2, Lactococcus lactis UTNGt28, and L. plantarum UTNGt21A, alone or in combination with EDTA (ethylenediaminetetraacetic acid) against multidrug-resistant Staphylococcus aureus ATCC1026 and Citrobacter freundii UTNB3Sm1. Based on the antimicrobial assay, among the 19 tested PCs, two (PC11 and PC17) produced a greater zone of inhibition against both pathogens in vitro. Time-killing assays indicated the rapid death of S. aureus after exposure to PC11 and PC17, while C. freundii was rapidly inhibited by PC11 and PC1 (UTNGt2 only), suggesting that the inhibitory action is pathogen and dose-dependent of a particular molecule present in the extract. A marginal inhibitory effect was observed when the peptides were combined with EDTA. Transmission electron microscopy (TEM) revealed the structural membrane damage of both target strains upon interaction with individual peptide extracts. Different degrees of cell deformation, condensed cytoplasm, membrane blebbing, and ghost cell formation with visibly broken cell walls were observed in S. aureus . Likewise, the separation of the cytoplasmic membrane from the outer membrane, ghost cells, along with ovoid and deformed cells with undulated cell walls were observed for C. freundii . Furthermore, scanning electronic microscopy (SEM) analysis revealed different wrinkled and deformed cells covered by debris. A leakage of aromatic molecules was detected for both pathogens, indicating that PCs disrupted the cell wall integrity, inducing cell death. Given their inhibitory action and capacity to induce damage of the cytoplasmic membrane, the selected PCs may serve to slow bacterial growth in vitro; further research is required to prove their efficiency ex vitro to battle against food poisoning and subsequent human infection.

Previously, we demonstrated that Heat Shock Protein 27 (HSP27) reduces the inflammatory stages of experimental atherogenesis, is released by macrophage (MΦ) exosomes and lowers cholesterol levels in atherosclerotic plaques. Recently, we discovered that natural autoantibodies directed against HSP27 enhance its signaling effects, as HSP27 immune complexes (IC) interact at the cell membrane to modulate signaling. We now seek to evaluate the potential role of the HSP27 IC on MΦ exosomal release and cholesterol export. First, in human blood samples, we show that healthy control subjects have 86% more exosomes compared to patients with coronary artery disease ( p < 0.0001). Treating human THP-1 MΦ with rHSP27 plus a validated anti-HPS27 IgG antibody increased the abundance of exosomes in the culture media (+98%; p < 0.0001) as well as expression of Flotillin-2, a marker reflective of exosomal release. Exosome cholesterol efflux was independent of Apo-A1. THP-1 MΦ loaded with NBD-labeled cholesterol and treated with the HSP27 IC showed a 22% increase in extracellular vesicles labeled with NBD and a 95% increase in mean fluorescent intensity. In conclusion, exosomal abundance and secretion of cholesterol content increases in response to HSP27 IC treatment, which may represent an important therapeutic option for diseases characterized by cholesterol accumulation.

A common problem in solar farms is to predict when accumulators stop working optimally and start losing efficiency. This paper proposes and describes how to use Bayesian networks together with expert systems to predict this moment by using a telecontrol multiagent system for monitoring solar farms with distributed sensors, which was developed in a previous work. To this end, a Bayesian network model and its implementation are proposed. The resulting system meets the requirements of telecontrol systems (reliability, flexibility, and response time), yields a solution for the prediction of lifespan batteries, and provides the multiagent system with autonomous intelligent capabilities and integrated learning.

Objective: Emerging evidence suggests that children with attention deficit and hyperactivity disorder (ADHD) present more difficulties in standing and walking balance than typically developing children. Most of previous studies have assessed these functions using postural and sensory organization tests showing differences in balance performance between control and ADHD children. However, to date, it is unknown whether these balance alterations are accompanied with vestibular dysfunction. The principal aim of this study is to evaluate vestibular otolith function in ADHD and matched control children., Methods: We assessed vestibular otolith function in children with ADHD and controls using the subjective visual vertical (SVV) bucket test and cervical vestibular-evoked myogenic potentials (cVEMPs). In addition, gait and balance were evaluated using the dynamic gait index (DGI) and computerized posturography., Results: Non-significant differences between groups were obtained in SVV evaluation. DGI results show lower scores for overall test performance in children with ADHD ( p  < 0.001), while computerized postural recordings showed significant differences for the limit of stability between groups ( p  = 0.02). cVEMPs in response to 500 Hz tone bursts presented at 100 dB were absent or reduced in children with ADHD, as revealed by differences in P1 and N1 peak-to-peak amplitudes between groups ( p  < 0.01)., Conclusion: These findings suggest that vestibular brainstem reflexes are altered in a subset of children with ADHD. We propose to include cVEMP reflexes in the clinical evaluation of ADHD patients.

In human breast cancer, β-catenin localization has been related with disease prognosis. Since HER2-positive patients are an important subgroup, and that in breast cancer cells a direct interaction of β-catenin/HER2 has been reported, in the present study we have explored whether β-catenin location is related with the disease survival. The study was performed in a tumor bank from patients (n = 140) that did not receive specific anti-HER2 therapy. The proteins were detected by immunohistochemistry in serial sections, 47 (33.5%) patients were HER2-positive with a long follow-up. HER2-positive patients that displayed β-catenin at the plasma membrane (completely surrounding the tumour cells) showed a significant better disease-free survival and overall survival than the patients showing the protein on other locations. Then we explored the dynamics of the co-expression of β-catenin and HER2 in human MCF-7 and SKBR3 cells exposed to different stressful situations. In untreated conditions MCF-7 and SKBR3 cells showed very different β-catenin localization. In MCF-7 cells, cadmium administration caused a striking change in β-catenin localization driving it from plasma membrane to cytoplasmic and perinuclear areas and HER2 showed a similar localization patterns. The changes induced by cadmium were compared with heat shock, H2O2 and tamoxifen treatments. In conclusion, this study shows the dynamical associations of HER2 and β-catenin and their changes in subcellular localizations driven by stressful situations. In addition, we report for the first time the correlation between plasma membrane associated β-catenin in HER2-positive breast cancer and survival outcome, and the importance of the protein localization in breast cancer samples.

In a recent study, we have shown that in mammary tumors from mice lacking the Cav-1 gene, there are alterations in specific heat shock proteins as well as in tumor development. With this in mind, we have now investigated other proteins in the same mammary mouse tumor model (Her-2/neu expressing mammary tumors from Cav-1 wild type and Cav-1 null mice), to further comprehend the complex tumor-stroma mechanisms involved in regulating stress responses during tumor development. In this tumor model the cancer cells always lacked of Cav-1, so the KO influenced the Cav-1 in the stroma. By immunohistochemistry, we have found a striking co-expression of β-catenin and Her-2/neu in the tumor cells. The absence of Cav-1 in the tumor stroma had no effect on expression or localization of β-catenin and Her-2/neu. Both proteins appeared co-localized at the cell surface during tumor development and progression. Since Her-2/neu activation induces MTA1, we next evaluated MTA1 in the mouse tumors. Although this protein was found in numerous nuclei, the absence of Cav-1 did not alter its expression level. In contrast, significantly more PTEN protein was noted in the tumors lacking Cav-1 in the stroma, with the protein localized mainly in the nuclei. P-Akt levels were relatively low in tumors from both Cav-1 WT and Cav-1 KO mice. There was also an increase in nuclear NHERF1 expression levels in the tumors arising from Cav-1 KO mice. The data obtained in the MMTV-neu model are consistent with a role for Cav-1 in adjacent breast cancer stromal cells in modulating the expression and localization of important proteins implicated in tumor cell behavior.

Hsp27 (HSPB1) is usually overexpressed in breast cancers affecting the disease outcome and the sensitivity of tumors to chemotherapy and radiotherapy. Hsp27 interacts with other proteins such as β-catenin, histone deacetylase HDAC6, transcription factor STAT2 and procaspase-3. Phosphatase and tensin homologue (PTEN) is a tumor suppressor gene that is deleted in many human tumors. The PI3K/Akt signaling pathway is negatively regulated by PTEN. Hsp27 is described as a key component of the Akt signaling cascade: Akt, BAD, Forkhead transcription factors, Hsp27, mitogen-activated protein kinase kinase-3 and -6. Here, we have examined whether the downregulation of Hsp27 by siHsp27 affects the PTEN levels in the MCF-7 human breast cancer cell line. PTEN was detected with two different antibodies using western blots and immunocytochemistry. p-Akt was also evaluated by western blot. In addition, Hsp27 and PTEN were immunoprecipitated to know whether these proteins interact. Intracellular colocalization studies were carried out by confocal microscopy. A significant reduction in the Hsp27 levels was noted in the siHsp27 transfected cells. These Hsp27 downregulated cells showed a significant increased expression of PTEN. The MW 76 and 55 kDa PTEN forms were upregulated as revealed by two different antibodies. The phosphatase activity of PTEN seems to be active because p-Akt levels were reduced. Hsp27 immunoprecipitation was bringing PTEN and vice versa, these two proteins seem to interact at cytoplasmic level by FRET. Downregulation of Hsp27 stabilized PTEN protein levels. Chaperone-assisted E3 ligase C terminus of Hsc70-interacting protein (CHIP) levels were not significantly influenced by Hsp27 downregulation. In conclusion, we report a novel function of Hsp27 modulating the PTEN levels in human breast cancer cells suggesting an interaction between these two molecules.

We have synthesized fourteen 3-phenylcoumarin derivatives and evaluated their anti-HIV activity. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as reporter. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Six compounds displayed NF-κB inhibition, four resulted Tat antagonists and three of them showed both activities. Three compounds inhibited HIV replication with IC₅₀ values < 25 µM. The antiviral effect of the 4-hydroxycoumarin derivative 19 correlates with its specific inhibition of Tat functions, while compound 8, 3-(2-chlorophenyl)coumarin, seems to act through a mechanism unrelated to the molecular targets considered in this research.

In the course of our search for antineoplasic agents from Panamanian Flora, two new alkylresorcinols: 1-(2,6-dihydroxyphenyl)octan-l-one (1) and (+)-1-(3-(1-(2,6-dihydroxyphenyl)butyl)-2,6-dihydroxyphenyl)octan-l-one (2), together with three known compounds, (1R, 2R)-l-(benzo[d][1,3]dioxol-5-yl)propane-1,2,3-triol (3), (+)-aptosimon (4) and (-)-sesamin (5), were identified from the leaves of Homalomena wendlandii Schott (Araceae). Their structures were established by 1D and 2D NMR and IR spectroscopic, and MS methods. Compound 2 exhibited IC50 values of 3.3, 5.8 and 4.0 microg/mL against MCF-7, SF-268 and H-460 cancer human cell lines, respectively.

The in vivo and in vitro effects of the pesticide endosulfan on the cholinesterase (ChE) activity were investigated in rats. ChE activity decreased in dams and in male pups within 65 days corresponding to 35% and 32% of inhibition respectively in the higher endosulfan dose (1.5 mg/kg). In vitro, the enzyme activity was found to be inhibited in a concentration dependent manner. The results suggest that endosulfan is able to inhibit the ChE activity and to cross the placental barrier and/or to be eliminated through milk affecting the enzyme activity in male rat pups.

Ethnopharmacological Relevance: Cecropia obtusifolia (Cecropiaceae) and Psychotria poeppigiana (Synonym: Cephaelis elata, Rubiaceae) are two Latin American plants broadly used in traditional Amerindian medicine. The former, together with many other species of the genus Cecropia, share the folk reputation of curing heart failure, cough, asthma and bronchitis. The latter is used in Panama by Kuna and Ngäbe Buglé (Guaymies) native Indians for the treatment of dyspnea., Aim of the Study: Based on screening of selected medicinal Panamanian plants by radioligand-binding techniques by Caballero-George et al. (2001), the present study was carried out in order to investigate the vasoactive effects of different fractions from both P. poeppigiana and C. obtusifolia on rat thoracic aorta and identify active fractions and their chemical constituents., Materials and Methods: Both acid and neutral methanol fractions (P-AMeOH and P-NMeOH) and acid and neutral dichlorometane fractions (P-ADCM and P-NDCM) were obtained from P. poeppigiana crude methanolic and dichlorometane extracts, respectively. Identical fractionation was carried out for C. obtusifolia (C-AMeOH, C-NMeOH, C-ADCM and C-NDCM. Vasorelaxant effect of all fractions, and their inhibition of contractile responses to angiotensin II were evaluated in isolated aortic rings., Results: P-AMeOH, P-NMeOH and P-ADCM fractions induced a concentration-dependent relaxation (43.9+/-1.8%, 35.3+/-4.7% and 52.9+/-3.5%, respectively) in the endothelium-intact aorta precontracted by phenylephrine (PE, 10(-6)M). The relaxation produced by C-AMeOH and C-NMeOH (57.3+/-2.5% and 53.3+/-3.3%, respectively) was greater than the effect produced by C-ADCM and C-NDCM (42.2+/-3.4% and 21.8+/-0.8%, respectively). Only the incubation of the aortic rings with P-AMeOH reduced the maximum contraction induced by angiotensin II at 20.08+/-0.55%., Conclusions: The direct vasorelaxation effect observed could explain in part the ethnomedical use of these plants in Amerindian traditional medicine. The most active fractions contain phenolic and aromatic acid compounds. Furthermore, P-AMeOH, the only fraction that showed both vasorelaxant effect and inhibition of contractile responses to angiotensin II, is the most rich in aromatic acids compounds and the only one that contains scopoletin., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to report 2 novel clinical cases of reactive lesions of the peri-implant mucosa associated with titanium dental implants where metal-like particles were observed histologically. In both cases, the lesions were diagnosed as epulis, based on clinical evidence. Extirpation biopsies were carried out. Case 1 was diagnosed as pyogenic granuloma and case 2 as peripheral giant cell granuloma. The presence of metal-like particles in the tissues suggests that the etiology of the lesions might be related to the corrosion process of the metal structure. This is the first case of pyogenic granuloma to be reported in association with dental implants. All clinical cases of soft tissue lesions associated with implants should be reported to contribute to the understanding of the etiology and pathogeny of these lesions., (Copyright 2009 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

The composition and biological activity of the essential oils from leaves, fruits, stems and bark of Protium confusum are reported for the first time. Forty-six to sixty-three constituents were identified ranging from 73.8% to 98.5% of the samples. Limonene (60.2%) was the main component in the fruit oil, whereas spathulenol (19.3%), beta-caryophyllene oxide (14.1%) and beta-caryophyllene (8.0%) reached the highest percentages in the oil from leaves. The volatile oils from bark and stems showed the same major constituents: p-cymen-8-ol (14.4% and 6.1%, respectively), spathulenol (9.5% and 9.0% respectively), and hexadecanoic acid (8.4% and 7.8%, respectively). The composition of the essential oils differed significantly from those of previously investigated Protium species. Three out of the four samples exhibited antibacterial activity against Staphylococcus aureus and Mycobacterium smegmatis, the one from leaves being the most active, with MIC values of 62.5 microg/mL in both cases. No activity against Candida albicans was detected. The bark oil showed the highest larvicidal activity against Aedes aegypti (LC100 = 125 microg/mL).

Ethnopharmacological Relevance: Dimerocostus strobilaceus is used by the Kuna Indians of Panama for the treatment of hypertension and other cardiovascular diseases., Aim of the Study: We investigated the vascular effects of acid and neutral fractions obtained from methanol and dichloromethane extracts of Dimerocostus strobilaceus., Materials and Methods: The acid and neutral methanol fractions (A-MeOH and N-MeOH) or acid and neutral dichlorometanic fractions (A-DCM and N-DCM) were tested using isolated rat aortic rings with or without endothelium pre-contracted by phenylephrine. We examined the ability of these different fractions at different concentrations to modify vascular responses induced by angiotensin II using endothelium-denuded aortic rings from Spontaneously Hypertensive Rats (SHR)., Results: In aortic rings with intact endothelium A-MeOH, N-MeOH and A-DCM fractions produced a concentration-dependent vasorelaxation (62.4 +/- 5.2, 64.5 +/- 5.0 and 63.7 +/- 5.0%, respectively), whereas the N-DCM fraction did not produce any vasorelaxant effect. Maximal relaxation evocated by vasoactive fractions was substantially inhibited on aortic rings without endothelium.Our study demonstrates that A-MeOH, N-MeOH, A-DCM and N-DCM significantly reduce contractile responses induced by angiotensin-II on aortic rings., Conclusions: Our findings may contribute to a better understanding of the potential link between vascular properties observed with Dimerocostus strobilaceus and their ethnobotanical use.

The aim of this study was to evaluate histologically the biological effect of pitting corrosion and to contribute clinically relevant data on the permanence of titanium metal structures used in osteosynthesis in the body. Commercially pure titanium laminar implants (control) and commercially pure titanium laminar implants with pitting corrosion (experimental) were implanted in the tibiae of rats. At 14 days post-implantation the animals were killed. The tibiae were resected, fixed, radiographed and processed for embedding in methyl methacrylate. Percentage of bone-implant contact and peri-implant bone volume were evaluated. The histological study of the titanium implants submitted to pitting corrosion showed scarce bone-implant contact, it was only present in the areas with no pitting and/or surface alterations. There was a statistically significant lower percentage of bone-implant contact in the experimental group (6%+/-4) than in the control group (26%+/-6) (p<0.001). Products of corrosion in the peri-implant bed, especially around the blood vessels and areas of bone marrow in the metal-tissue interface, were observed. The microchemical analysis of corrosion products revealed the presence of titanium. The adverse local effects caused by pitting corrosion suggest that titanium plates and grids should be used with caution as permanent fixation structures.

Bioassay-guided fractionation of the chloroform and ethanol extracts of Tovomita longifolia leaves using cytotoxic and antimicrobial assays resulted in the isolation of four new benzophenones, (E)-3-(2-hydroxy-7-methyl-3-methyleneoct-6-enyl)-2,4,6-trihydroxybenzophenone (1), (E)-3-(6-hydroxy-3,7-dimethylocta-2,7-dienyl)-2,4,6-trihydroxybenzophenone (2), 8-benzoyl-2-(4-methylpenten-3-yl)chromane-3,5,7-triol (3), and 5-benzoyl-1,1,4a-trimethyl-2,3,4,4a,9,9a-hexahydro-1H-xanthene-6,8-diol (4), and two known benzophenones, 4-geranyloxy-2,6-dihydroxybenzophenone (5) and 3-geranyl-2,4,6-trihydroxybenzophenone (6). The structures of 1-4 were established by spectroscopic means and by molecular modeling calculations. Compounds 1 and 3-5 demonstrated cytotoxic activities against breast (MCF-7), central nervous system (SF-268), and lung (H-460) human cancer cell lines, while compounds 3-6 showed antimicrobial activity against Klebsiella pneumoniae, Mycobacterium smegmatis, Pseudomonas aeruginosa, Salmonella gallinarum, and Staphylococcus aureus.

Mutations in different exons of ret proto-oncogene are responsible for the development of medullary thyroid carcinoma (MTC). The mutations can occur as sporadic or as part of multiple endocrine neoplasia (MEN) type 2 hereditary syndromes. Here we report the first focused study of sporadic MTC in Brazilian patients regarding clinical and molecular analysis of ret proto-oncogene. Our study seeks to estimate the risk of hereditary MTC cases among apparently sporadic cases in a Brazilian population and describe ret genetic variants in their germinative lineage. Germinative sequence variants were screened by DNA sequencing and denaturing gradient gel electrophoresis (DGGE) analysis of exons 10, 11, 13, 14, 15, and 16 of 24 Brazilian patients with apparently sporadic MTC. We identified 1 inherited case of 24 (4%) patients with apparently sporadic MTC. Polymorphisms for the ret proto-oncogene coding region were identified in codon 769 of exon 13 (LeuCTT--> LeuCTG) at a frequency of 13% (3/24) and in codon 904 of exon 15 (SerTCC--> SerTCG) at a frequency of 16.6% (4/24). The observed frequency (4%) of inherited disease among apparent sporadic MTC strengthens routine application of ret proto-oncogene germinative DNA screening in all cases of apparently sporadic MTC ascertained at Brazilian cancer hospitals.

A new lignan, 3,4,5'-trimethoxy-3',4'-methylenedioxy-7,9':7',9 diepoxylignan (1) (6-[4-(3,4-dimethoxy-phenyl)-tetrahydro-furo[3,4-c.]furan-1-yl]-4-methoxy-benzo[ ] dioxole) together with two known lignans, 7'-epi.-sesartemin (2) and diayangambin (3), and a known flavonoid, 5-hydroxy-7,4'-dimethoxyflavone (4), were isolated from the leaves of Piper fimbriulatum. C. DC. Their structures were assigned by a combination of one- and two-dimensional NMR techniques. 7'-epi.-Sesartemin (2) showed the highest larvicidal activity against Aedes aegypti. (LC 100 17.6 µg/ml) and weak antiplasmodial (IC 50 7.0 µg/ml) and antitrypanosomal (IC 50 39.0 µg/ml) activities. None of the compounds was active against Leishmania mexicana..

The use of odontological or orthopedic metal implants requires the availability of techniques to estimate tissue response to the corrosion processes. In previous experimental studies we showed the deposition of corrosion products not only locally (Olmedo et al., Implant Dent 2003; 12: 75-80) but also systemically (Olmedo et al., J Mater Sci: Mater in Medic 2002; 13: 793-796) in organs such as liver, spleen and lung. The aim of the present study was to propose a method to quantitatively assess the tissue deposits of the corrosion products of the materials used to manufacture implants. The samples (liver and lung) were embedded in paraffin, and the histological sections were submitted to thickness standardization. The quantitative evaluation of the deposits was performed in an MPM-800 (Carl Zeiss)* microscope. The light microscopy images were digitalized and then analyzed employing the DNA-IBAS-Kontron software that allows for the identification and evaluation of cells loaded with corrosion products (objective 20x). The following end-points were assessed: total field area, number of deposits of corrosion products, partial and total area of the deposits, and the ratio between volume of the deposits and tissue volume. The method proposed serves to quantitatively evaluate, at light microscopy level, the deposition of corrosion products in tissues.

Purpose: The aim of this study was to evaluate, histologically and quantitatively, the presence of macrophages loaded with metallic particles in the periimplant soft tissues of failed titanium (Ti) dental implants., Materials and Methods: The study was performed on sections of metallic Ti implants embedded in methyl methacrylate resin that exhibited macrophages in the soft tissues contiguous with the implant. The volume of periimplant soft tissue was evaluated, and the number of macrophages was determined. The particles within macrophages were analyzed by energy-dispersive x-ray analysis., Results: Macrophages were more abundant in the zone adjacent to the metallic implant as compared with the zone further away from the implant. Energy-dispersive x-ray analysis revealed the presence of Ti within macrophages., Conclusions: Macrophages loaded with Ti particles can be associated with a corrosion process. The method proposed would allow for the objective evaluation of the presence of macrophages associated with dental implants and other orthopedic materials that contain Ti or other metals.

Metallic implants can generate and release titanium oxide (TiO(2)) and zirconium oxide (ZrO(2)) to the tissues. These products can accumulate locally or disseminate systemically. The aim of the present study was to assess the distribution of TiO(2) and ZrO(2) administered intraperitoneally to rats. We used male Wistar rats of approximately 100 g body weight throughout the study. An intraperitoneal injection of a suspension of TiO(2) or ZrO(2) (16, 1600 and 16 x 10(3) mg/kg body weight) was administered. The animals were killed at 5-10 months post-administration by ether overdose. Samples of peritoneum, liver, kidney, lung and spleen were taken, fixed in formalin and routine processed for embedding in paraffin. One set of sections was stained with hematoxylin and eosin and another set was prepared unstained. The presence of titanium in the tissues was detected by X-ray diffraction crystallography. The histological analysis revealed the presence of abundant intracellular aggregates of metallic particles of Ti and Zr in peritoneum, liver, lung and spleen. The crystallographic study revealed the presence of anatasa. The dissemination of metallic particles from orthopedic or odontological implants would not be restricted to a local phenomenon. The particles also target vital organs. The distribution of these deposits over lengthy periods deserves meticulous attention given the clinical relevance of this phenomenon.

Among the local and systemic factors affecting bone repair, great interest is focused on age and gender. The aim of this work was to perform a histomorphometric evaluation of peri-implant bone healing response in male and female rats aged 1 and 3 months. Forty Wistar rats were i.p. anesthetized with xylazine and ketamine. A c.p. Ti implant (Implant Vel, Buenos Aires-Argentina) was placed in the right tibia following the method described by Cabrini et al. (Implant Dent 1993; 2:264-267). Group I: (GI, n = 10) female rats aged 1 month; Group II: (GII, n = 10) female rats aged 3 months; Group III: (GIII, n = 10) male rats aged 1 month; Group IV: (GIV, n = 10) male rats aged 3 months. All the animals were killed by ether overdose 30 days post-implantation. The tibiae were resected, radiographed and embedded in methyl-methacrylate. Ground sections perpendicular to the longer axis of the tibia were obtained and stained with toluidine blue. Percentage of osseointegration and peri-implant bone tissue volume were evaluated. No differences in peri-implant bone tissue histology were observed among groups. No statistically significant differences in peri-implant bone volume and percentage of osseointegration were observed between GII (adult females) and GIV (adult males). Peri-implant bone volume and percentage of osseointegration were markedly greater in GIV (adult males) than in GIII (young males) (14 +/- 1 mm2 and 8 +/- 2 mm2) p < 0.01 and (49 +/- 6% and 24 +/- 9%) p < 0.01 respectively. Using this experimental model, differences in peri-implant osteogenesis (bone volume and percentage of osseointegration) associated to gender were only observed in the young rats, and differences associated to age were found between the groups of males.

The aim of this study was to evaluate the effects of experimental diabetes on the healing period leading to osseointegration. Wistar rats were injected with a single dose of streptozotocin (STZ); body weight and food intake were assessed every 48 hours. On days 2, 12, 26, and 42 post-STZ, glucemia, plasma hemoglobin, and urea were determined. Twelve days post-STZ, a titanium laminar implant was placed in the right tibia of each rat. Two groups of 20 rats each were killed on days 14 and 30 postimplantation, respectively. Results (ANOVA test) showed STZ-treated rats to have 1) a significant decrease in body weight; 2) an increase in food intake; 3) normal hemoglobin and plasma urea values; 4) a significant increase in glucemia; and 5) a decrease in tibiae length. Microscopic evaluation 14 days postimplantation revealed the presence of woven bone, and, at 30 days, laminar bone was in contact with the implant. Our findings show that, in this model of periimplant bone repair and under the experimental conditions stated herein, STZ-induced diabetes retards periimplant bone healing.

Corrosion phenomena would appear to play a decisive role in metallic implant long term behaviour. This study presents a method to correlate results obtained in "in vivo" and "in vitro" studies on materials used for metallic implants. Samples of titanium and copper immersed in saline solution (pH 7.4 and 5.2) were used for the "in vitro" study. Implants of these same materials were placed in rat tibiae following the method previously described by Cabrini et al. The animals were killed 14 days post-implantation, the tibiae were resected, radiographed and embedded in acrylic resin. Polarization curves revealed high corrosion in copper implants and low corrosion in titanium implants. It is important to point out that the titanium samples suffered slightly higher corrosion when immersed in a lower pH medium (pH 5.2), as in chronic inflammatory processes. A passive film was found on titanium samples as opposed to the strong corrosion observed in the copper implants. Microscopy revealed osseointegration around titanium implants and a severe inflammatory reaction with abscesses surrounding the copper implants. The method presented herein would allow to correlate "in vivo" and "in vitro" studies on corrosion in different implant materials and establish their relation with cell response.