Antiviral activity of plants occurring in the state of minas gerais (Brazil): Part III

A total of 24 extracts from 14 plant species collected at the state of Minas Gerais, Brazil, and belonging to five botanical families (Annonaceae, Apocynaceae, Ochnaceae, Polygonaceae and Vitaceae) was screened for cytotoxicity in cultured Vero cells and for antiviral activity against human herpes virus type 1 (HSV-1), vaccinia virus (VACV) and murine encephalomyocarditis virus (EMCV). The highest cytotoxicity (CC 50 < 10 μg/mL) was observed for the ethanol extracts from Annona coriacea fruits and seeds. Extracts from Hancornia speciosa, Ouratea castaneafolia and O. semisrrata were the only ones that have shown activity against all the three viruses assayed. Extracts from Polygonum spectabile, Hancornia speciosa, Himatanthus phagedaenica, Ouratea spectabilis and O. semiserrata were the most active against HSV-1 (EC 50 < 50 mg/mL), with favorable SI values (8.0 to 10.0). Hancornia speciosa and Anaxagorea dolichocarpa were the most active against EMCV (EC 50 50 - 100 μg/mL), with reasonable SI values (5.2 to 6.1), while moderate to low activity (EC 50 > 100 μg/mL) was observed for Ouratea spectabilis and O. semiserrata. A total of 7 plant species, Ouratea semiserrata, O. spectabilis, O. castanaeafolia, Rollinia laurifolia, Cissus erosa, Polygonum spectabile, and Hancornia speciosa, were active against VACV, disclosing EC50 < 50 μg/mL and SI values ranging from 6.6 to 67.3. In total, 10 out of the 14 species were selected from a literature survey on plants used to treat viral diseases in Brazil; these species were responsible for 70% of the positive results.

Surface-enhanced Raman scattering (SERS) applied to cancer diagnosis and detection of pesticides, explosives, and drugs

The inelastic scattering of light, Raman scattering, presents a very low cross section. However, the signal can be amplified by several orders of magnitude, leading to the so-called surface-enhanced Raman scattering (SERS) phenomenon. Basically, the SERS effect is achieved when the target molecule (analyte) is adsorbed onto metallic nanoparticles, usually noble metals. This article presents an overview of the applications of SERS to cancer diagnosis and the detection of pesticides, explosives, and drugs (illicit and pharmacological). SERS is routinely applied nowadays to detect and identify analytes at very low concentrations, including for single-molecule detection. However, the application of SERS as an analytical tool requires reliable and reproducible SERS substrates, in terms of enhancement factors, which depends on the size, shape, and aggregation of the metallic nanoparticles. Therefore, the production of reliable and reproducible SERS substrates is a challenge in the field. Besides, the metallic nanoparticles can also induce changes in the system by possible interactions with the analyte under investigation, which must be taken into account. This review will present work in which, under certain specific experimental conditions, SERS has been analytically applied.

Nasal administration of liquid crystal precursor mucoadhesive vehicle as an alternative antiretroviral therapy

The purpose of this study was to develop a mucoadhesive stimuli-sensitive drug delivery system for nasal administration of zidovudine (AZT). The system was prepared by formulating a low viscosity precursor of a liquid crystal phase, taking advantage of its lyotropic phase behavior. Flow rheology measurements showed that the formulation composed of PPG-5-CETETH-20, oleic acid and water (55, 30, 15% w/w), denominated P, has Newtonian flow behavior. Polarized light microscopy (PLM) revealed that formulation P is isotropic, whereas its 1:1 (w/w) dilution with artificial nasal mucus (ANM) changed the system to an anisotropic lamellar phase (PD). Oscillatory frequency sweep analysis showed that PD has a high storage modulus (G′) at nasal temperatures. Measurement of the mucoadhesive force against excised porcine nasal mucosa or a mucin disk proved that the transition to the lamellar phase tripled the work of mucoadhesion. Ex vivo permeation studies across porcine nasal mucosa exhibited an 18-fold rise in the permeability of AZT from the formulation. The Weibull mathematical model suggested that the AZT is released by Fickian diffusion mechanisms. Hence, the physicochemical characterization, combined with ex vivo studies, revealed that the PPG-5-CETETH-20, oleic acid, and water formulation could form a mucoadhesive matrix in contact with nasal mucus that promoted nasal absorption of the AZT. For an in vivo assessment, the plasma concentrations of AZT in rats were determined by HPLC method following intravenous and intranasal administration of AZT-loaded P formulation (PA) and AZT solution, respectively, at a dose of 8 mg/kg. The intranasal administration of PA resulted in a fast absorption process (Tmax = 6.7 min). Therefore, a liquid crystal precursor formulation administered by the nasal route might represent a promising novel tool for the systemic delivery of AZT and other antiretroviral drugs. In the present study, the uptake of AZT absorption in the nasal mucosa was demonstrated, providing new foundations for clinical trials in patients with AIDS. © 2012 Elsevier B.V. All rights reserved.

In Vitro Susceptibility of Environmental Isolates of Exophiala dermatitidis to Five Antifungal Drugs

Several dematiaceous fungi frequently isolated from nature are involved in cases of superficial lesions to lethal cerebral infections. Antifungal susceptibility data on environmental and clinical isolates are still sparse despite the advances in testing methods. The objective of this study was to examine the activities of 5-flucytosine, amphotericin B, itraconazole, voriconazole and terbinafine against environmental isolates of Exophiala strains by minimum inhibition concentration (MIC) determination. The strains were obtained from hydrocarbon-contaminated soil, ant cuticle and fungal pellets from the infrabuccal pocket of attine gynes. Broth microdilution assay using M38-A2 reference methodology for the five antifungal drugs and DNA sequencing for fungal identification were applied. Terbinafine was the most active drug against the tested strains. It was observed that amphotericin B was less effective, notably against Exophiala spinifera, also studied. High MICs of 5-flucytosine against Exophiala dermatitidis occurred. This finding highlights the relevance of studies on the antifungal resistance of these potential opportunistic species. Our results also contribute to a future improvement of the standard methods to access the drug efficacy currently applied to black fungi. © 2012 Springer Science+Business Media Dordrecht.

Effects of constant rate infusion of anesthetic or analgesic drugs on general anesthesia with isoflurane: A retrospective study in 200 dogs

Constant rate infusion (CRI) shows several advantages in balanced anesthesia, such as reduction of requirement for inhaled anesthetics and control of pain. The most commonly used drugs in these protocols are local anesthetics, dissociative, and opioids, which may be administered alone or in combinations. We evaluated the records of 200 dogs that underwent various surgical procedures with anesthetic or analgesic CRI in the perioperative period during 2011 and 2012 at the Veterinary Hospital of Franca University (Unifran), and identified possible complications during the transoperative period. Records evaluated included clinical state, laboratory tests, drugs used in premedication and induction, and CRI protocol. Acepromazine and morphine were the main drugs used in premedication. Propofol was used to induce anesthesia alone or in combination with other agents. We evaluated records of the 25 different CRI protocols. Fentanyl was the main drug employed in CRI, either alone or in combination. There were 128 episodes of anesthetic complications during CRI;the most common were hypotension, hypertension, and tachycardia, which occurred in 43 (32%), 35 (26.3%), and 19 (14.2%) dogs, respectively. Cardiac arrhythmia was reported in only 4 dogs. Signs of respiratory depression were present in dogs treated with 6 different CRI protocols. The consumption of isoflurane (vol %) reduced between 15.7% and 21.05% after 30minutes of the CRI in the fentanyl and fentanyl-lidocaine-ketamine CRI groups (p<0.05). In conclusion, CRI is a valid component of balanced anesthesia in dogs, safe, and has a low incidence of adverse effects. However, future studies are warranted to describe the results of the clinical use of CRI to better characterize and refine this technique.

Genotoxic evaluation of the antimalarial drugs artemisinin and artesunate in human HepG2 cells and effects on CASP3 and SOD1 gene expressions

The malaria treatment recommended by the World Health Organization involves medicines derived from artemisinin, an active compound extracted from the plant Artemisia annua, and some of its derivatives, such as artesunate. Considering the lack of data regarding the genotoxic effects of these compounds in human cells, the objective of this study was to evaluate the cytotoxicity and genotoxicity, and expressions of the CASP3 and SOD1 genes in a cultured human hepatocellular liver carcinoma cell line (HepG2 cells) treated with artemisinin and artesunate. We tested concentrations of 2.5, 5, 7.5, 10, and 20 μg/mL of both substances with a resazurin cytotoxicity assay, and the concentrations used in the genotoxicity experiments (2.5, 5, and 10 μg/mL) and gene expression analysis (5 mg/mL) were determined. The results of the comet assay in cells treated with artemisinin and artesunate showed a significant dosedependent increase (P < 0.001) in the number of cells with DNA damage at all concentrations tested. However, the gene expression analysis revealed no significant change in expression of CASP3 or SOD1. Our data showed that although artemisinin and artesunate exhibited genotoxic effects in cultured HepG2 cells, they did not significantly alter expression of the CASP3 and SOD1 genes at the doses tested. ©FUNPEC-RP.

Variabilidade da protease NS3 do vírus da hepatite C e avaliação das mutações de resistência em pacientes não tratados com inibidores de protease

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Influência da tecnologia educacional na avaliação do conhecimento de portadores de hepatite C crônica sobre sua doença e aderência ao tratamento antiviral

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Biochemical and nutritional evaluation of patients with visceral leishmaniasis before and after treatment with leishmanicidal drugs

Introduction Visceral leishmaniasis (VL) is caused by the intracellular protozoan Leishmania donovani complex. VL may be asymptomatic or progressive and is characterized by fever, anemia, weight loss and the enlargement of the spleen and liver. The nutritional status of the patients with VL is a major determinant of the progression, severity and mortality of the disease, as it affects the clinical progression of the disease. Changes in lipoproteins and plasma proteins may have major impacts in the host during infection. Thus, our goal was evaluate the serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, glucose, albumin, globulin and total protein levels, as well as the body composition, of VL patients before and after treatment. Methods Nutritional evaluation was performed using the bioelectrical impedance analysis (BIA) to assess body composition. Biochemical data on the serum total cholesterol, HDL, LDL, triglycerides, glucose, albumin, globulin and total protein were collected from the medical charts of the patients. Results BIA indicated that both pre-treatment and post-treatment patients exhibited decreased phase angles compared to the controls, which is indicative of disease. Prior to treatment, the patients exhibited lower levels of total body water compared to the controls. Regarding the biochemical evaluation, patients with active VL exhibited lower levels of total cholesterol, HDL, LDL and albumin and higher triglyceride levels compared to patients after treatment and the controls. Treatment increased the levels of albumin and lipoproteins and decreased the triglyceride levels. Conclusions Our results suggest that patients with active VL present biochemical and nutritional changes that are reversed by treatment.

Anti dermatophytic therapy: prospects for the discovery of new drugs from natural products

Millions of people and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which only infect keratinized structures. With the appearance of AIDS, the incidence of dermatophytosis has increased. Current drug therapy used for these infections is often toxic, long-term, and expensive and has limited effectiveness; therefore, the discovery of new anti dermatophytic compounds is a necessity. Natural products have been the most productive source for new drug development. This paper provides a brief review of the current literature regarding the presence of dermatophytes in immunocompromised patients, drug resistance to conventional treatments and new anti dermatophytic treatments.

Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit

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

Glutathione-s-transferase modified electrodes for detecting anticancer drugs

With the fast growth of cancer research, new analytical methods are needed to measure anticancer drugs. This is usually accomplished by using sophisticated analytical instruments. Biosensors are attractive candidates for measuring anticancer drugs, but currently few biosensors can achieve this goal. In particular, it is challenging to have a general method to monitor various types of anticancer drugs with different structures. In this work, a biosensor was developed to detect anticancer drugs by modifying carbon paste electrodes with glutathione-s-transferase (GST) enzymes. GST is widely studied in the metabolism of xenobiotics and is a major contributing factor in resistance to anticancer drugs. The measurement of anticancer drugs is based on competition between 1-chloro-2,4-dinitrobenzene (CDNB) and the drugs for the GST enzyme in the electrochemical potential at 0.1 V vs. Ag/AgCl by square wave voltammetry (SWV) or using a colorimetric method. The sensor shows a detection limit of 8.8 mu M cisplatin and exhibits relatively long life time in daily measurements. (C) 2014 Elsevier B.V. All rights reserved.

Hypusine Modification of the Ribosome-binding Protein eIF5A, a Target for New Anti-Inflammatory Drugs: Understanding the Action of the Inhibitor GC7 on a Murine Macrophage Cell Line

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

Antiplatelet and Antithrombotic Activities of Non-Steroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit

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

Peptide Prodrugs for the Treatment of CNS Disorders: A Perspective for New Drugs

The treatment of central nervous system (CNS) diseases is a major challenge. The presence of the barrier intended to protect the brain from unwanted molecules also impairs the efficacy of CNS-targeted drugs. The discovery of drug targets for CNS diseases opens a door for the selective treatment of these diseases. However, the physicochemical properties of drugs, including their hydrophilic properties and their peripheral metabolism, as well as the blood-brain barrier, can adversely affect the therapeutic potential of CNS-targeted drugs. Although peptides are often metabolized by enzymes, they are of particular interest for the treatment of CNS diseases or as carriers to deliver drugs to the brain. In this review, we discuss the use of peptides as potential prodrugs for the treatment of CNS diseases.