Citral: A monoterpene with prophylactic and therapeutic anti-nociceptive effects in experimental models of acute and chronic pain

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Stress Abolishes the Effect of Previous Chronic Ethanol Consumption on Drug Place Preference and on the Mesocorticolimbic Brain Pathway

BackgroundConditioned place preference (CPP) to ethanol (EtOH) is an important addiction-related alteration thought to be mediated by changed neurotransmission in the mesocorticolimbic brain pathway. Stress is a factor of major importance for the initiation, maintenance, and reinstatement of drug abuse and modulates the neurochemical outcomes of drugs. Thus, the aim of this study was to investigate the effects of concomitant exposure to chronic EtOH and stress on CPP to this drug and alterations of dopaminergic and serotonergic neurotransmission in mice.MethodsMale Swiss mice were chronically treated with EtOH via a liquid diet and were exposed to forced swimming stress. After treatment, animals were evaluated for conditioning, extinction, and reinstatement of CPP to EtOH. Also, mice exposed to the same treatment protocol had their prefrontal cortex (PFC), nucleus accumbens (NAc), and amygdala dissected for the quantitation of dopamine, serotonin, and their metabolites content.ResultsData showed that previous chronic exposure to EtOH potentiated EtOH conditioning and increased dopaminergic turnover in PFC. Exposure to stress potentiated EtOH conditioning and decreased dopaminergic turnover in the NAc. However, animals exposed to both chronic EtOH and stress did not display alterations of CPP and showed an elevated content of dopamine in amygdala. No treatment yielded serotonergic changes.ConclusionsThe present study indicates that previous EtOH consumption as well as stress exposure induces increased EtOH conditioning, which can be related to dopaminergic alterations in the PFC or NAc. Interestingly, concomitant exposure to both stimuli abolished each other's effect on conditioning and PFC or NAc alterations. This protective outcome can be related to the dopaminergic increase in the amygdala.

Nanotechnology-based drug delivery systems and herbal medicines: a review

Herbal medicines have been widely used around the world since ancient times. The advancement of phytochemical and phytopharmacological sciences has enabled elucidation of the composition and biological activities of several medicinal plant products. The effectiveness of many species of medicinal plants depends on the supply of active compounds. Most of the biologically active constituents of extracts, such as flavonoids, tannins, and terpenoids, are highly soluble in water, but have low absorption, because they are unable to cross the lipid membranes of the cells, have excessively high molecular size, or are poorly absorbed, resulting in loss of bioavailability and efficacy. Some extracts are not used clinically because of these obstacles. It has been widely proposed to combine herbal medicine with nanotechnology, because nano-structured systems might be able to potentiate the action of plant extracts, reducing the required dose and side effects, and improving activity. Nanosystems can deliver the active constituent at a sufficient concentration during the entire treatment period, directing it to the desired site of action. Conventional treatments do not meet these requirements. The purpose of this study is to review nanotechnology- based drug delivery systems and herbal medicines.

Effects of P-MAPA immunomodulator on Toll-like receptor 2, ROS, nitric oxide, MAPKp38 and IKK in PBMC and macrophages from dogs with visceral leishmaniasis

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

Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Heteropterys tomentosa (A. Juss.) infusion counteracts Cyclosporin a side effects on the ventral prostate

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

Low Dose of the Anesthetic Propofol Does Not Induce Genotoxic or Mutagenic Effects in Nile Tilapia

We demonstrate the efficacy of propofol (2,6-diisopropylphenol) as an anesthetic when administered to fish in an immersion bath and show the absence of genetic side effects following short-term exposure to the drug. All tested fish were anesthetized (as indicated by loss of posture and lack of response to physical stimulation), and both the comet assay (tail intensity) and the micronucleus assay revealed that propofol does not induce primary DNA damage or chromosome damage in the fish Nile Tilapia Oreochromis niloticus. Our results should be considered in light of our particular test conditions, including the water temperature (similar to 25 degrees C), the life stage and size of the fish, and the single exposure to the anesthetic. We suggest that propofol is a promising anesthetic in terms of its lack of genotoxic effects, at least in low dosages in adult Nile Tilapia.Received June 25, 2013; accepted October 15, 2013

Glycosomal Targets for Anti-Trypanosomatid Drug Discovery

Glycosomes are peroxisome-related organelles found in all kinetoplastid protists, including the human pathogenic species of the family Trypanosomatidae: Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. Glycosomes are unique in containing the majority of the glycolytic/gluconeogenic enzymes, but they also possess enzymes of several other important catabolic and anabolic pathways. The different metabolic processes are connected by shared co-factors and some metabolic intermediates, and their relative importance differs between the parasites or their distinct life-cycle stages, dependent on the environmental conditions encountered. By genetic or chemical means, a variety of glycosomal enzymes participating in different processes have been validated as drug targets. For several of these enzymes, as well as others that are likely crucial for proliferation, viability or virulence of the parasites, inhibitors have been obtained by different approaches such as compound libraries screening or design and synthesis. The efficacy and selectivity of some initially obtained inhibitors of parasite enzymes were further optimized by structure-activity relationship analysis, using available protein crystal structures. Several of the inhibitors cause growth inhibition of the clinically relevant stages of one or more parasitic trypanosomatid species and in some cases exert therapeutic effects in infected animals. The integrity of glycosomes and proper compartmentalization of at least several matrix enzymes is also crucial for the viability of the parasites. Therefore, proteins involved in the assembly of the organelles and transmembrane passage of substrates and products of glycosomal metabolism offer also promise as drug targets. Natural products with trypanocidal activity by affecting glycosomal integrity have been reported.

Development and characterization of biocompatible isotropic and anisotropic oil-in-water colloidal dispersions as a new delivery system for methyl dihydrojasmonate antitumor drug

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effects of Photodynamic Therapy with Blue Light and Curcumin as Mouth Rinse for Oral Disinfection: A Randomized Controlled Trial

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of different mydriatics on intraocular pressure, pupil diameter, and ruminal and intestinal motility in healthy sheep

Objective To determine the effects of the administration of subconjunctival 1% atropine (SA), topical 1% atropine (A), 0.5% tropicamide (T), 1% homatropine (H), 10% phenylephrine (P), and 2% ibopamine (I) on intraocular pressure (IOP), pupil diameter (PD), ruminal motility (RM) and intestinal motility (IM) in sheep.Animal studied Ten spayed ewes of Santa Ines breed.Procedures Six experiments were performed separately at 1-week intervals. One eye was randomly selected and received one drop of A, T, H, P, I, or subconjunctival injection of atropine at 8 a. m. On the following days, IOP and PD were evaluated every 8 h until the pupil returned to its normal diameter. Ruminal motility and intestinal motility were evaluated only within the first 13 h.Results The IOP did not change significantly in the treated eyes compared with the control eyes and baseline at any time point (P > 0.05). A longer-lasting pupil dilation was observed after the administration of A (96 h), SA (79 h), H (24 h), and T (24 h). Within the first 30 min after treatment, RM and IM decreased, by 78% and 82% (H), 76% and 86% (SA), 46% and 58% (A), and 62% and 70% (T) (P < 0.001), respectively, with a tendency to return to baseline values following 13 h of drug administration. Both 10% phenylephrine and 2% ibopamine did not have any effect on the parameters evaluated (P > 0.05).Conclusions Topical and subconjunctival 1% atropine, 0.5% tropicamide, and 1% homatropine significantly reduced RM and IM, and induced pupil dilation but did not change IOP in eyes of healthy sheep. The sympathomimetics phenylephrine (10%) and ibopamine (2%) did not change the parameters evaluated.

Design and Characterization of Silicone and Surfactant Based Systems for Topical Drug Delivery

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

Positive effects of auditory cue in locomotor pattern of people with Parkinson's disease (off and on medication)

Gait disorders are identified in people with Parkinson’s disease. The aim of this study was to investigate the effect of auditory cues and medication on kinematic, kinetic and EMG parameters, during different gait phases of people with PD and healthy elderly. Thirty subjects distributed in two groups (Group 1, PD patients off and on medication; Group 2, healthy elderly) participated in this study and were instructed to walk in two experimental conditions: non-cued and cued. Therefore, kinematic, kinetic and electromyography analyses were utilized to investigate the locomotor pattern. Changes in locomotor pattern (greater muscular activity) with auditory cue were observed for PD patients. Regarding the medication, locomotor parameter improvement was observed after levodopa intake in association with the auditory cue. These results confirm the hypothesis about the external cues therapy that could be used as a complement to drug therapy to achieve improvement in the locomotor pattern of PD patients.

Immunomodulatory effects of low dose chemotherapy and perspectives of combanation with immunotherapy

Nowadays cancer is one of the main causes of death and many efforts worldwide have been driven to find out new treatments and approaches in order to extinguish or reduce this group of disorder. Chemotherapy is the main treatment for cancer, however, conventional schedule based on maximum tolerated dose (MTD) show several side effects and frequently allow the development of drug resistance. In this review we present the evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics is as efficient as MTD and works better in some situations. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provide us the evidence that low concentrations of selected chemotherapeutics agents, rather than conventional high doses, should be chosen for combination with immunotherapy

Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblasts

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)