ABSTRACT
Medical reports indicate a prevalence of pain in 50% of patients with cancer. In this context, this article investigated the antinociceptive activity of α-PHE using in vivo Sarcoma-180-induced hypernociception in mice to detail its mechanism(s) of antinociception under different conditions of treatment and tumor progression. Firsty, in vitro cytotoxic action was assessed using melanoma B-16/F-10 and S-180 murine cells and colorimetric MTT assays. For in vivo studies, acute treatment with α-PHE (6.25, 12.5, 25 and 50 mg/kg orally by gavage) was performed on the 1st day after S-180 inoculation. Subacute treatments were performed for 8 days starting on the next day (early protocol) or on day 8 after S-180 inoculation (late protocol). For all procedures, mechanical nociceptive evaluations were carried out by von Frey's technique in the subaxillary region peritumoral tissue (direct nociception) and in right legs of S-180-bearing mice (indirect nociception). α-PHE showed in vitro cytotoxic action on B-16/F-10 and S-180 (CI50 values of 436.0 and 217.9 µg/mL), inhibition of in vivo tumor growth (ranging from 47.3 to 82.7%) and decreased direct (peritumoral tissue in subaxillary region) and indirect (right leg) mechanical nociception in Sarcoma 180-bearing mice with early and advanced tumors under acute or subacute conditions of treatment especially at doses of 25 and 50 mg/kg. It improved serum levels of GSH as well as diminished systemic lipid peroxidation, blood cytokines (interleukin-1ß, -4, -6, and tumor necrosis factor-α). Such outcomes highlight α-PHE as a promising lead compound that combines antinociceptive and antineoplasic properties. Its structural simplicity make it a cost-effective alternative, justifying further mechanistic investigations and the development of pharmaceutical formulations. Moreover, the protocols developed and standardized here make it possible to use Sarcoma-180 hypernociception model to evaluate the capacity of new antinociceptive molecules under conditions of cancer-related allodynia.
Subject(s)
Analgesics/pharmacology , Antineoplastic Agents/pharmacology , Cancer Pain/drug therapy , Cyclohexane Monoterpenes/pharmacology , Melanoma, Experimental/drug therapy , Sarcoma 180/drug therapy , Animals , Cancer Pain/etiology , Cancer Pain/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cytokines/metabolism , Female , Glutathione/metabolism , Inflammation Mediators/metabolism , Lipid Peroxidation/drug effects , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice , Pain Threshold , Sarcoma 180/complications , Sarcoma 180/metabolism , Sarcoma 180/pathology , Tumor Burden/drug effects , Tumor Cells, CulturedABSTRACT
INTRODUCTION: Microemulsions are thermodynamically stable translucent systems widely used for systemic delivery of drugs. The present study is the first to analyze the biotechnological potential of microemulsion systems for therapeutic purposes, through transdermal route, for pain treatment. AREAS COVERED: Patents were searched in the World Intellectual Property Organization (WIPO), European Patent Office (Espacenet), United States Patent and Trademark Office (USPTO) and National Institute of Intellectual Property (INPI). The inclusion criteria were published patents containing the keywords; 'microemulsion' and 'transdermal' in their title or abstract. 208 patents were found. However, only those patents which mentioned in their abstract or in their description the use of microemulsion system (object of invention) for pain treatment were selected. Were excluded duplicate patents and those that did not report pharmacological use of MEs specifically for pain treatment. Thus, sixteen patents were selected and described in the present study. EXPERT OPINION: Patents were found that focused specifically on the development process of microemulsion systems, the inclusion of essential oils in microemulsions, which place microemulsions as delivery systems for NSAIDs and other substances, as well as microemulsions for transdermal administration. These studies reinforce the therapeutic applicability of MEs in the treatment of acute and chronic pain.
Subject(s)
Drug Delivery Systems , Drug Design , Pain/drug therapy , Administration, Cutaneous , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Biotechnology , Emulsions , Humans , Oils, Volatile/chemistry , Patents as Topic , ThermodynamicsABSTRACT
Standard lipoprotein measurements of triglycerides, total cholesterol, low-density lipoproteins (LDL), and high-density lipoproteins (HDL) fail to identify many lipoprotein abnormalities that contribute to cardiovascular heart diseases (CHD). Studies suggested that the presence of CHD is more strongly associated with the HDL subspecies than with total HDL cholesterol levels. The HDL particles can be collected in at least three subfractions, the HDL2b, HDL2a, and HDL3. More specifically, atherosclerosis is associated with low levels of HDL2. In this work, the optical spectroscopic properties of europium tetracycline (EuTc) complex in the presence of different HDL subspecies was studied. The results show that the europium spectroscopic properties in the EuTc complex are influenced by sizes and concentrations of subclasses. Eu3+ emission intensity and lifetime can discriminate the subfractions HDL3 and HDL2b.
Subject(s)
Europium/chemistry , Lipoproteins, HDL/blood , Lipoproteins, HDL/chemistry , Spectrometry, Fluorescence/methods , Tetracyclines/chemistry , Humans , Lipoproteins, HDL/classificationABSTRACT
Antimicrobial photodynamic therapy (APDT) may become a useful clinical tool to treat microbial infections, and methylene blue (MB) is a well-known photosensitizer constantly employed in APDT studies, and although MB presents good efficiency in antimicrobial studies, some of the MB photochemical characteristics still have to be evaluated in terms of APDT. This work aimed to evaluate the role of MB solvent's ionic strength regarding dimerization, photochemistry, and photodynamic antimicrobial efficiency. Microbiological survival fraction assays on Escherichia coli were employed to verify the solution's influence on MB antimicrobial activity. MB was evaluated in deionized water and 0.9% saline solution through optical absorption spectroscopy; the solutions were also analysed via dissolved oxygen availability and reactive oxygen species (ROS) production. Our results show that bacterial reduction was increased in deionized water. Also we demonstrated that saline solution presents less oxygen availability than water, the dimer/monomer ratio for MB in saline is smaller than in water and MB presented a higher production of ROS in water than in 0.9% saline. Together, our results indicate the importance of the ionic strength in the photodynamic effectiveness and point out that this variable must be taken into account to design antimicrobial studies and to evaluate similar studies that might present conflicting results.
Subject(s)
Anti-Infective Agents/pharmacology , Methylene Blue/pharmacology , Photochemotherapy/methods , Sodium Chloride/chemistry , Water/chemistry , Bacterial Load/drug effects , Bacterial Load/radiation effects , Escherichia coli/drug effects , Escherichia coli/radiation effects , Osmolar Concentration , Oxygen/chemistry , Photochemical Processes , Photosensitizing Agents/pharmacology , Reactive Oxygen Species/chemistry , Solvents/chemistry , Spectrum AnalysisABSTRACT
Random lasing in nanocrystalline Nd(3+):YVO(4) powder is demonstrated. A method that analyzes the decay kinetics after long-pulse excitation is used to determine the laser characteristics. This method permits to measure the fractional contribution of spontaneous and stimulated emission as well as upconversion as a function of the pump intensity. We observed that maximum linewidth narrowing is achieved when the stimulated emission reaches 50% of fractional contribution in the backscattering cone.
Subject(s)
Lasers, Solid-State , Nanostructures/chemistry , Crystallization , Equipment Design , Equipment Failure AnalysisABSTRACT
We report here the observation, for the first time, of the enhancement of Europium-Tetracycline complex emission in cholesterol solutions. This enhancement was initially observed with the addition of the enzyme cholesterol oxidase, which produces H(2)O(2), the agent driver of the Europium tetracycline complex, to the solution. However, it was found that the enzyme is not needed to enhance the luminescence. A calibration curve was determined, resulting in a simple method to measure the cholesterol quantity in a solution. This method shows that the complex can be used as a sensor to determine cholesterol in biological systems.
Subject(s)
Cholesterol/metabolism , Europium/chemistry , Fluorescent Dyes/chemistry , Organometallic Compounds/chemistry , Tetracycline/chemistry , Cholesterol Oxidase/metabolism , Europium/metabolism , Luminescence , Organometallic Compounds/metabolism , Spectrometry, Fluorescence , Tetracycline/metabolismABSTRACT
The aim of this study was to investigate the ability of malachite green (MG) combined with a low-power red laser to kill Actinobacillus actinomycetemcomitans and to investigate MG photodegradation after photodynamic therapy (PDT) by optical absorption spectroscopy. The etiology of periodontal disease is that microorganisms form a bacterial biofilm on the surface of the teeth. It is an infectious disease and A. actinomycetemcomitans is considered an important agent in biofilm ecology. Instead of using antibiotics, PDT is an alternative approach to eradicate bacteria. Cultures of A. actinomycetemcomitans were exposed to a 30 mW diode red laser, in the presence or absence of MG. A group of cultures was treated in dark conditions in the presence of MG (0.01% w/v) for 5 min. In the presence of MG, two exposure times for laser irradiation were used: t=3 min (energy dose=5.4 J/cm(2)), and t=5 min (energy dose=9 J/cm(2)). The samples were diluted and bacterial colonies were counted and converted into colony forming units. Absorption spectra of the bacterial suspensions, MG, MG-stained bacterial suspensions, and photosensitized bacterial suspensions were obtained. A. actinomycetemcomitans can be photoinactivated by a red laser in the presence of MG. Significant differences were observed between the two energy doses used (p<0.05). Red laser alone and MG alone were not able to kill bacteria. Optical absorption showed that MG is photobleached after irradiation. These results indicate that A. actinomycetemcomitans can be photosensitized by red laser combined with MG and that the dye is photodegraded following irradiation.
Subject(s)
Aggregatibacter actinomycetemcomitans/drug effects , Photochemotherapy/methods , Rosaniline Dyes/pharmacology , Aggregatibacter actinomycetemcomitans/radiation effects , Bacteriological Techniques , Drug Stability , Humans , Lasers , Periodontal Diseases/etiology , Periodontal Diseases/microbiology , Periodontal Diseases/therapy , Rosaniline Dyes/radiation effects , Rosaniline Dyes/therapeutic useABSTRACT
We introduce the use of a lanthanide complex, tetracycline-europium, for the clinical diagnosis of urea hydrogen peroxide in human whole blood. The values obtained agree with the urea concentration variation verified in 49 patients, including 12 predialysis, 12 peritoneal, and 15 dialysis subjects, and 10 controls. This method is noninvasive and can help in the identification of renal and cardiac diseases.
Subject(s)
Molecular Probes/chemistry , Organometallic Compounds/chemistry , Peroxides/blood , Tetracyclines/chemistry , Urea/analogs & derivatives , Biosensing Techniques/methods , Carbamide Peroxide , Drug Combinations , Fluorescence , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Renal Dialysis , Reproducibility of Results , Sensitivity and Specificity , Urea/bloodABSTRACT
An increase in the europium emission band was observed, for the first time, with addition of urea hydrogen peroxide to the tetracycline-europium (Tc-Eu)solution. We have observed that the wavelength, the band width and the area of 5D0-->7F2 europium transition change with the urea hydrogen peroxide concentration. We claim that the tetracycline-europium complexes can be used as probes of urea hydrogen peroxide concentration.
