Distribution of neutral prilocaine in a phospholipid bilayer: Insights from molecular dynamics simulations

In this work, we report a 20-ns constant pressure molecular dynamics simulation of prilocaine (PLC), in amine-amide local anesthetic, in a hydrated liquid crystal bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine. The partition of PLC induces the lateral expansion of the bilayer and a concomitant contraction in its thickness. PLC molecules are preferentially found in the hydrophobic acyl chains region, with a maximum probability at similar to 12 angstrom from the center of the bilayer (between the C(4) and C(5) methylene groups). A decrease in the acyl chain segmental order parameter, vertical bar S-CD vertical bar, compared to neat bilayers, is found, in good agreement with experimental H-2-NMR studies. The decrease in vertical bar S-CD vertical bar induced by PLC is attributed to a larger accessible volume per lipid in the acyl chain region. (C) 2008 Wiley Periodicals, Inc.

Stability and Local Toxicity Evaluation of a Liposomal Prilocaine Formulation

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Preferential location of prilocaine and etidocaine in phospholipid bilayers: A molecular dynamics study

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

Distribution of neutral prilocaine in a phospholipid bilayer: Insights from molecular dynamics simulations

In this work, we report a 20-ns constant pressure molecular dynamics simulation of prilocaine (PLC), in amine-amide local anesthetic, in a hydrated liquid crystal bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine. The partition of PLC induces the lateral expansion of the bilayer and a concomitant contraction in its thickness. PLC molecules are preferentially found in the hydrophobic acyl chains region, with a maximum probability at similar to 12 angstrom from the center of the bilayer (between the C(4) and C(5) methylene groups). A decrease in the acyl chain segmental order parameter, vertical bar S-CD vertical bar, compared to neat bilayers, is found, in good agreement with experimental H-2-NMR studies. The decrease in vertical bar S-CD vertical bar induced by PLC is attributed to a larger accessible volume per lipid in the acyl chain region. (C) 2008 Wiley Periodicals, Inc.

Stability and Local Toxicity Evaluation of a Liposomal Prilocaine Formulation

This study reports a physicochemical stability evaluation of a previously reported liposomal prilocaine (PLC(LUV)) formulation (Cereda el al. J. Pharm. Pharmaceut. Sci. 7:235, 2004) before and after steam sterilization as well as its local toxicity evaluation. Prilocaine (PLC) was encapsulated into extruded unilamellar liposomes (LUVs) composed by egg phosphatidylcholine:cholesterol:alfa-tocopherol (4:3:0.07, mole %). Laser light-scattering analysis (p > 0.05) and thiobarbituric acid reaction (p > 0.05) were used to evaluate the liposomes physical (size) and chemical (oxidation) stability, respectively. The prilocaine chemical stability was followed by (1)H-nuclear magnetic resonance. These tests detected no differences on the physicochemical stability of PLC or PLCLUV, sterilized or not, up to 30 days after preparation (p > 0.05). Finally, the paw edema test and histological analysis of rat oral mucosa were used to assess the possible inflammatory effects of PLC(LUV). PLC(LUV) did not evoke rat paw edema (p > 0.05), and no significant differences were found in histological analysis, when compared to the control groups (p > 0.05). The present work shows that PLC(LUV) is stable for a 30-day period and did not induce significant inflammatory effects both in the paw edema test and in histological analysis, giving supporting evidence for its safely and possible clinical use in dentistry.

Preferential location of prilocaine and etidocaine in phospholipid bilayers: A molecular dynamics study

In this work, we report a 20-ns constant pressure molecular dynamics simulation of the uncharged form of two amino-amide local anesthetics (LA). etidocaine and prilocaine, present at 1:3 LA:lipid, molar ratio inside the membrane, in the hydrated liquid crystal bilayer phase of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC). Both LAs induced lateral expansion and a concomitant contraction in the bilayer thickness. A decrease in the acyl chain segment order parameter, -S(CD), compared to neat bilayers, was also observed. Besides, both LA molecules got preferentially located in the hydrophobic acyl chains region, with a maximum probability at similar to 12 and similar to 10 angstrom from the center of the bilayer for prilocaine and etidocaine, respectively. (C) 2009 Elsevier B.V. All rights reserved.

Takayasu's arteritis: What should the dentist know?

Takayasu's arteritis is a chronic inflammatory disease that affects large blood vessels, especially the aorta and/or its major branches. The condition presents with segmental lesions adjacent to normal, apparently unaffected, areas. The lesions include stenosis, occlusion, dilatations or aneurysm formations along the path of the affected artery. Because of the severity of the disease and the possibility of cardiovascular complications, patients with Takayasu's arteritis require medical treatment based on immunosuppressive and antihypertensive drugs, as well as regular follow up and surgical intervention in many instances. The aim of this paper was to describe the characteristics of Takayasu's arteritis, to report dental treatment carried out on an affected patient, and to discuss the main implications and care required during routine treatment for children in the dental office. © 2005 BSPD and IAPD.

Effect of Arnica montana 6 cH on edema, mouth opening and pain in patients submitted to extraction of impacted third molars

This study had the objective to evaluate the homeopathic action of Arnica montana 6 cH and placebo on edema, mouth opening (trismus) and pain in patients submitted to extraction of bilaterally impacted lower third molars. The experiment was carried out as a crossover and double-blind study. The data showed that edema was significantly reduced by the treatment with Arnica montana 6 cH (p<0.05) and did not demonstrate significant effect on trismus and pain as compared to control group.

Avaliação do tipo de procedimento odontológico, cirurgia x dentística restauradora, na variabilidade do tempo de duração de dois anestésicos: bupivacaína x prilocaína

Pós-graduação em Odontologia - ICT

Estudio histológico del processo de reparación alveolar después de la aplicación tópica de la solucioón anestésica prilocaína 3 % con felipressina o,o3 ui/ml

The aim of this study was to evaluate the local anesthetic solution, composed by Prilocaine 3% and felipressin 0,03 UI/ml, influence on the alveolar repair process in rats after dental extraction. This research was previously approved by the Ethic Committee in Research of the Masters Degree Program in Oral and Maxillofacial Surgery of the Marília University (UNIMAR), Marília, São Paulo, Brazil. It was an experimental, randomly controlled study, with bifactorial analysis (group control versus experimental group, in function of the postoperative times (2 X 4)). For the accomplishment of this study 32 rats were used (Rattus norvegicus, albinus, Wistar), males, adults, weighing between 280 and 320 grams. The animals were selected and divided into Group I (control) and Group II (Citocain 3%® - Prilocaine 3% with felipressin 0,03UI/ml) with 16 rats each; being four animals of the Group I and four of the Group II, destined to the euthanasia in the postoperative periods of 3rd, 7th, 15th and 24th days. The histological analysis with base in the developed methodology, allowed us to conclude that the anesthetic solution of Citocain 3%® applied with gauze compress on the surgical dental wound, produced tissue events that committed the basic biological principles, that are responsible for the regeneration of the gingival epithelium and the alveolar process repair in rats. The Group I presented better results in the alveolar repair when compared to the Group II.

Felypressin Increases Blood Pressure During Dental Procedures in Hypertensive Patients

Background: Felypressin has been added to local anesthetic to increase the length of the anesthetic effect and reduce toxicity during dental procedures. However, the effect on blood pressure remains uncertain, and this may be highly relevant in the dental treatment of hypertensive patients. Objective: To investigate the effect of felypressin on blood pressure in hypertensive patients with controlled BP. Methods: 71 subjects with these characteristics and in need of periodontal treatment were studied. After 10 minutes of rest, local anesthesia (prilocaine) was infiltrated with and without addition of felypressin. Then, a deep subgingival scaling was performed. Blood pressure was measured by an automated oscillometric device (DIXTAL DX2010). Ten minutes after the administration of the anesthetic, peak anesthetic action was recorded. The State-Trait Anxiety Inventory (STAI) was used to assess the patients' trait anxiety. Results: Systolic blood pressure increased after anesthesia, regardless of association with felypressin, throughout the dental procedure (p<0.05) and this response can be explained, at least in part, by the trait anxiety levels of the subjects. However, a further increase in diastolic blood pressure was observed when prilocaine was associated with felypressin (p<0.05), but this response did not change with trait anxiety levels. Conclusion: Felypressin increased the diastolic blood pressure of hypertensive patients with controlled blood pressure. Patients with high trait anxiety presented increases in systolic blood pressure upon some procedures, suggesting that an increase in blood pressure might also be related to fear or anxiety. (Arq Bras Cardiol 2012;99(2):724-731)

Multivariate spectroscopic methods for the analysis of solutions

In this thesis some multivariate spectroscopic methods for the analysis of solutions are proposed. Spectroscopy and multivariate data analysis form a powerful combination for obtaining both quantitative and qualitative information and it is shown how spectroscopic techniques in combination with chemometric data evaluation can be used to obtain rapid, simple and efficient analytical methods. These spectroscopic methods consisting of spectroscopic analysis, a high level of automation and chemometric data evaluation can lead to analytical methods with a high analytical capacity, and for these methods, the term high-capacity analysis (HCA) is suggested. It is further shown how chemometric evaluation of the multivariate data in chromatographic analyses decreases the need for baseline separation. The thesis is based on six papers and the chemometric tools used are experimental design, principal component analysis (PCA), soft independent modelling of class analogy (SIMCA), partial least squares regression (PLS) and parallel factor analysis (PARAFAC). The analytical techniques utilised are scanning ultraviolet-visible (UV-Vis) spectroscopy, diode array detection (DAD) used in non-column chromatographic diode array UV spectroscopy, high-performance liquid chromatography with diode array detection (HPLC-DAD) and fluorescence spectroscopy. The methods proposed are exemplified in the analysis of pharmaceutical solutions and serum proteins. In Paper I a method is proposed for the determination of the content and identity of the active compound in pharmaceutical solutions by means of UV-Vis spectroscopy, orthogonal signal correction and multivariate calibration with PLS and SIMCA classification. Paper II proposes a new method for the rapid determination of pharmaceutical solutions by the use of non-column chromatographic diode array UV spectroscopy, i.e. a conventional HPLC-DAD system without any chromatographic column connected. In Paper III an investigation is made of the ability of a control sample, of known content and identity to diagnose and correct errors in multivariate predictions something that together with use of multivariate residuals can make it possible to use the same calibration model over time. In Paper IV a method is proposed for simultaneous determination of serum proteins with fluorescence spectroscopy and multivariate calibration. Paper V proposes a method for the determination of chromatographic peak purity by means of PCA of HPLC-DAD data. In Paper VI PARAFAC is applied for the decomposition of DAD data of some partially separated peaks into the pure chromatographic, spectral and concentration profiles.