Liquid Chromatography-Tandem Mass Spectrometry Method for Detection and Quantification of Meloxicam and 5'-Carboxymeloxicam in Oral Fluid Samples.

A sensitive, selective and particularly fast method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of meloxicam and its main metabolite, 5'-carboxymeloxicam, in oral fluid samples. Meloxicam and its major metabolite were separated using a Shim-Pack XR-ODS 75 L × 2.0 column and C18 pre-column at 40 °C using a mixture of methanol and 10 mM ammonium acetate (80:20, v/v) with an injection flow rate of 0.3 mL/min. The total time of the analytical run was 5 min. Sixteen volunteers had oral fluid samples collected sequentially before and after taking a meloxicam tablet (15 mg) for up to 96 h. With the concentrations obtained, the pharmacokinetic parameters were determined using the Phoenix WinNonlin software. The parameters evaluated for meloxicam and 5'-carboxymeloxicam in the oral fluid samples showed linearity, accuracy, precision, medium-quality control (MQC-78.12 ng/mL), high-quality control (HQC-156.25 ng/mL), lower limits of quantification (LLOQ-0.6103 ng/mL), low-quality control (LQC-2.44 ng/mL), stability and dilution. Prostaglandin E2 (PGE2) was also detected and quantified in the oral fluid samples, demonstrating the possibility of a pharmacokinetic/pharmacodynamic (PK/PD) study with this methodology. All the parameters evaluated in the validation of the methodology in the oral fluid samples proved to be stable and within the possible variations in each of the described parameters. Through the data presented, the possibility of a PK/PD study was demonstrated, detecting and quantifying meloxicam, its main metabolite and PGE2 in oral fluid samples using LC-MS/MS.

Simultaneous separation of naproxen and 6-O-desmethylnaproxen metabolite in saliva samples by liquid chromatography-tandem mass spectrometry: Pharmacokinetic study of naproxen alone and associated with esomeprazol-Results.

After performing liquid-liquid extraction with ethyl acetate and HCl, samples from 12 volunteers who performed sequential collections after taking a tablet of naproxen alone (n = 6) or associated with esomeprazole (n = 6) were analyzed in a triple quadrupole mass spectrometer 8040 LC MS/MS Shimadzu. Separation of naproxen and its main metabolite 6-O-desmethylnaproxen was performed in a Shim-Pack XR-ODS 75Lx2.0 column and C18 pre-column at 40°C using a mixture of methanol and ammonium acetate 10 mM (70:30, v/v) with an injection rate of 0.3 ml/min. The total analytical run time for each sample was 5 min. The association of naproxen with esomeprazole take considerably longer time to reach the maximum concentration [Tmax 0.17 h (interquartile range, 0.13-1.95) for naproxen alone and 13.18*h (interquartile range, 10.12-27.15) for naproxen with esomeprazole, p = 0.002], also to be eliminated [T1/2 0.12 h (interquartile range, 0.09-1.35) for naproxen alone and 9.16*h (interquartile range, 7.16-41.40) for naproxen with esomeprazole, p = 0.002] and lower maximum concentrations (Cmax 4.6 ± 2.5 ug/mL for naproxen alone and 2.04 ± 0.78* µg/mL, p = 0.038). The association of naproxen with esomeprazole showed increased values of AUC0-t [82.06* h*µg/mL (interquartile range, 51.90-157.00) with esomeprazole and 2.97 h*µg/mL (interquartile range, 1.82-7.84) naproxen alone, p = 0.002] in drug concentrations in relation to the naproxen tablet alone, probably, such differences are due to the delay in the absorption of naproxen when it is associated with the drug proton pump inhibitor, esomeprazole. As well as reduced values of full clearance when naproxen is combined with esomeprazole (0.07* µg/h (interquartile range, 0.005-0.01) with esomeprazole and 7.29 µg/h (interquartile range, 3.17-16.23) in naproxen alone, p = 0.002). Both naproxen and 6-O-desmethylnaproxen in saliva samples can be effectively quantified using LC-MS/MS, this methodology proved to be rapid, sensitive, accurate and selective for each drug and allows for the analysis of their pharmacokinetic parameters, in both situations.

CYP2C9 Polymorphism Influence in PK/PD Model of Naproxen and 6-O-Desmethylnaproxen in Oral Fluid.

Polymorphisms in CYP2C9 can significantly interfere with the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of nonsteroidal anti-inflammatory drugs (NSAIDs), including naproxen. The present research aimed to study the PK/PD parameters of naproxen and its metabolite, 6-O-desmethylnaproxen, associated with allelic variations of CYP2C9. In our study, a rapid, selective, and sensitive Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method was developed and validated for the determination of naproxen and its main metabolite, 6-O-desmethylnaproxen, in oral fluid. Naproxen and its main metabolite were separated using a Shim-Pack XR-ODS 75L × 2.0 column and C18 pre-column at 40 °C using a mixture of methanol and 10 mM ammonium acetate (70:30, v/v), with an injection flow of 0.3 mL/min. The total analytical run time was 3 min. The volunteers, previously genotyped for CYP2C9 (16 ancestral­CYP2C9 *1 and 12 with the presence of polymorphism­CYP2C9 *2 or *3), had their oral fluids collected sequentially before and after taking a naproxen tablet (500 mg) at the following times: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6 8, 11, 24, 48, 72 and 96 h. Significant differences in the PK parameters (* p < 0.05) of naproxen in the oral fluid were: Vd/F (L): 98.86 (55.58−322.07) and 380.22 (261.84−1097.99); Kel (1/h): 0.84 (0.69−1.34) and 1.86 (1.09−4.06), in ancestral and mutated CYP2C9 *2 and/or *3, respectively. For 6-O-desmethylnaproxen, no PK parameters were significantly different between groups. The analysis of prostaglandin E2 (PGE2) proved to be effective and sensitive for PD parameters analysis and showed higher levels in the mutated group (p < 0.05). Both naproxen and its main metabolite, 6-O-desmethylnaproxen, and PGE2 in oral fluid can be effectively quantified using LC-MS/MS after a 500 mg oral dose of naproxen. Our method proved to be effective and sensitive to determine the lower limit of quantification of naproxen and its metabolite, 6-O-desmethylnaproxen, in oral fluid (2.4 ng/mL). All validation data, such as accuracy, precision, and repeatability intra- and inter-assay, were less than 15%. Allelic variations of CYP2C9 may be considered relevant in the PK of naproxen and its main metabolite, 6-O-desmethylnaproxen.

Detection and quantification of prostaglandin E2 in saliva by liquid chromatography-tandem mass spectrometry using microextraction by packed sorbent.

The detection of eicosanoids in saliva samples can assist pharmacokinetic/pharmacodynamic studies due to the facility of obtaining samples, minimal discomfort and high adherence of volunteers to the study. The present study enabled determine prostaglandin E2 concentrations in saliva samples, using a microextraction by packed sorbent methodology and subsequent detection in liquid chromatography-tandem mass spectrometry. Twelve volunteers underwent scaling and coronary-radicular polishing of the upper molars and sequential saliva collections: 0.25-96 h after ingestion of a 600 mg ibuprofen tablet, to quantify prostaglandin E2 concentrations. There was an increase in the level of prostaglandin E2 with a significant difference after the dental procedure (0.25 h) compared to 11, 24, 48 and 72 h (*p < 0.05). After taking the drug, these levels begin to decrease up to 5 h, returning to normal in the subsequent hours. The method was developed and validated with linearity between 2.4 and 1250 ng/mL and r2 above 0.9932. The limit of quantitation was about 2.4 ng/mL. The coefficients of variation and the relative standard errors of the accuracy and precision analyzes were < 15%. The proposed extraction and analysis methodology proved to be efficient, fast and promising for pharmacokinetic/pharmacodynamic assays after using anti-inflammatory drugs.

Analysis of Different Methods of Extracting NSAIDs in Biological Fluid Samples for LC-MS/MS Assays: Scoping Review.

The aim of this study was to carry out a systematic investigation and analysis of different drug extraction methods, specifically non-steroidal anti-inflammatory drugs in biological fluid samples, for Liquid Chromatography in Mass Spectrometry assays (LC-MS/MS). A search was carried out in the main databases between 1999 and 2021, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. Data were obtained through PubMed, Lilacs, Embase, Scopus, and Web of Science databases using the Boolean operators AND and OR. Studies were pre-selected by title and abstract by two independent reviewers. The selected texts were read in full, and only those that were complete and compatible with the inclusion and exclusion criteria were eligible for this research. A total of 248 references were obtained in the databases. After removing the duplicates and analyzing the titles and abstracts, 79 references were evaluated and passed to the next phase, which comprised the complete reading of the article. A total of 39 publications were eligible for this study. In 52% of the studies, the authors used the liquid-liquid extraction method (LLE), while in 41%, the solid-phase extraction method (SPE) was used. A total of 5% used microextraction methods and 2% used less-conventional techniques. The literature on the main methods used, the LLE and SPE methods, is extensive and consolidated; however, we found other studies that reported modifications of these traditional techniques, which were equally validated for use in LC-MS/MS. From this review, it is concluded that the diversity of techniques, reliability, and practical information about each analytical method used in this study can be adapted to advances in LC-MS/MS techniques; however, more ecological, economic, and sustainable approaches should be explored in the future.

Multifocal Analysis of Acute Pain After Third Molar Removal.

Background: To analyze the pain modulation capacity profile in a Brazilian population, the relationship between opioid receptor (OPRM1) and Catechol-O-methyltransferase (COMT) 1polymorphisms and pain modulation capacity was determined through preoperative pain modulation tests and acute postoperative pain control evaluation, swelling, and trismus in 200 volunteers undergoing lower third molar removal. Methods: Psychologic and clinical parameters were measured. Patient DNA was sequenced for single nucleotide polymorphisms in OPRM1 and COMT, and the salivary concentration of interleukin (IL)-2 (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α was evaluated. Primary outcomes were the influence of all predictors on the fluctuation of pain intensity using a visual analogue scale (VAS), and swelling and trismus on the 2nd and 7th postoperative days. Preoperative pain modulation capacity (CPM), pain catastrophizing scale (PCS), body mass index (BMI), and surgery duration and difficulty were evaluated. Results: Salivary concentration of IFN-γ and IL-2 as well as the duration of surgery influenced the fluctuation of postoperative pain in the VAS, and in the sum of the differences in pain intensity test at 8, 48, and 96 h. BMI influenced swelling, while both BMI and COMT haplotype influenced trismus on the 2nd postoperative day. Conclusion: Polymorphisms in COMT, salivary concentrations of IL-2 and IFN-γ, BMI, and duration of surgery were predictors for pain fluctuation, swelling, and trismus on the 2nd day after lower third molar extraction. This therapy was effective in controlling inflammatory symptomatology after lower third molar extraction and ibuprofen was well tolerated by patients. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03169127.

Pharmacogenetic and Pharmacokinetic Assays from Saliva Samples Can Guarantee Personalized Drug Prescription.

Saliva is widely used for clinical and laboratory analysis. This study proposed to use DNA extracted from saliva for genotyping and pharmacokinetics of piroxicam. A fast and efficient genotyping method was used to determine relevant allelic variants of CYP2C9 (*2 and *3), since genetic factors can influence in non-steroidal anti-inflammatory drugs (NSAIDs) metabolization. DNA Extract All Reagents Kit® was used for DNA extraction and genotyping was performed using TaqMan® GTXpress™ Master Mix, SNP genotyping assays and a Viia7 Real-Time PCR system. Volunteers performed sequential collections of saliva samples before and after taking a single dose of piroxicam (0.25 to 72 h) which were used for pharmacokinetics assays. Piroxicam concentrations were analyzed using LC-MS/MS. Sixty-six percent of volunteers were ancestral homozygous (CYP2C9*1/*1), and 34% showed one or both polymorphisms. Of these 34%, 22 individuals showed CYP2C9*2 polymorphism, 8 CYP2C9*3, and 4 CYP2C9*2/*3. Piroxicam pharmacokinetics were performed in 5 subjects. Areas under the curve (AUC0-t(h*ng/mL)) for CYP2C9*1/*1, *1/*2 and *1/*3 were, respectively, 194.33±70.93, 166 and 303. Maximum concentrations (Cmax(ng/mL)) for these genotypes were respectively 6.46±2.56, 4.3 and 10.2. Saliva sampling was a very effective matrix for both pharmacogenetic and pharmacokinetic tests, ensuring the speed of the procedure and the well-being and agreement of the participants. Once having the knowledge about the slow and fast metabolizers, it is possible to make an adequate prescription in order to avoid the adverse effects of the medication and to guarantee greater analgesic comfort to the patients respectively.

Losartan and isoproterenol promote alterations in the local renin-angiotensin system of rat salivary glands.

Renin-angiotensin system (RAS) systemically or locally collaborates with tissue homeostasis, growth and development, which has been extensively studied for its pharmacological implications. This study was primarily aimed at finding and characterizing local RAS in rat parotid, sublingual and submandibular glands. It was also hypothesized that vasoactive drugs could affect the expression of RAS targets, as well as saliva flow and its composition. Therefore, another objective of this study was to compare the effects of losartan (angiotensin II receptor blocker) and isoproterenol (ß-adrenergic receptor agonist). Forty-one Wistar rats were divided into three groups and administered a daily intraperitoneal dose of saline, losartan or isoproterenol solutions for one week. The following RAS targets were studied using qPCR: renin (REN), angiotensinogen (AGT), angiotensin converting enzyme (ACE), ACE-2, elastase-2 (ELA-2), AT1-a and MAS receptors, using RPL-13 as a reference gene. Morphology of glands was analyzed by immunohistochemistry using REN, ACE, ACE-2, AT1, AT2 and MAS antibodies. The volume and total protein content of saliva were measured. Our results revealed that ACE, ACE-2, AT1-a, AT2 and MAS receptors were expressed in all salivary gland samples, but REN and ELA-2 were absent. Losartan decreased mRNA expression of RAS targets in parotid (MAS) and submandibular glands (ACE and both AT receptors), without affecting morphological alterations, and significantly decreased saliva and total protein secretions. Isoproterenol treatment affected gene expression profiles in parotid (ACE, ACE-2, AT1-a, MAS, AGT), and submandibular (ACE, AT2, AGT) glands, thus promoting acinar hypertrophy in serous acini, without significant changes in salivary flow or total protein content. These drugs affected mainly acini, followed by duct systems and myoepithelial cells, whereas blood vessels were not affected. In conclusion, there is a local RAS in major rat salivary glands and losartan, an angiotensin II receptor blocker, affected not only the RAS-target gene expression but also decreased salivary flow and total protein content.

Temporomandibular disorders and painful comorbidities: clinical association and underlying mechanisms.

The association between temporomandibular disorders (TMDs) and headaches, cervical spine dysfunction, and fibromyalgia is not artefactual. The aim of this review is to describe the comorbid relationship between TMD and these three major painful conditions and to discuss the clinical implications and the underlying pain mechanisms involved in these relationships. Common neuronal pathways and central sensitization processes are acknowledged as the main factors for the association between TMD and primary headaches, although the establishment of cause-effect mechanisms requires further clarification and characterization. The biomechanical aspects are not the main factors involved in the comorbid relationship between TMD and cervical spine dysfunction, which can be better explained by the neuronal convergence of the trigeminal and cervical spine sensory pathways as well as by central sensitization processes. The association between TMD and fibromyalgia also has supporting evidence in the literature, and the proposed main mechanism underlying this relationship is the impairment of the descending pain inhibitory system. In this particular scenario, a cause-effect relationship is more likely to occur in one direction, that is, fibromyalgia as a risk factor for TMD. Therefore, clinical awareness of the association between TMD and painful comorbidities and the support of multidisciplinary approaches are required to recognize these related conditions.

Effective method for the detection of piroxicam in human plasma using HPLC.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used by the general population to alleviate inflammation and pain after oral surgeries. Piroxicam is among the most commonly used NSAIDs and excels in controlling pain, swelling, trismus and other common symptoms of inflammation. This study aimed to evaluate different concentrations of piroxicam and its major metabolite, 5'-hydroxypiroxicam, in human plasma samples over time using high performance liquid chromatography (HPLC) after liquid-liquid extraction. Briefly, 10 volunteers participated in this study after approval by the Ethics Committee of Bauru School of Dentistry, Universidade de São Paulo - USP, Brazil. Volunteers received a single dose oral of piroxicam (20 mg) and had blood collected at various times following an established protocol. The methodology of liquid-liquid extraction was effective for determining concentrations of piroxicam in plasma using HPLC in 10 out of 10 volunteers while 5'-hydroxypiroxicam was only detected in 2 out of 10 volunteers.

Quantification of piroxicam and 5'-hydroxypiroxicam in human plasma and saliva using liquid chromatography-tandem mass spectrometry following oral administration.

Saliva sampling used to quantify piroxicam and 5'-hydroxypiroxicam is a noninvasive and painless method when compared to sequential blood sampling. For that, a rapid, selective and sensitive liquid chromatography-tandem mass spectrometric method for simultaneous determination of piroxicam and 5'-hydroxypiroxicam in saliva and human plasma was developed and validated. Piroxicam and its major metabolite were separated using a LiChroCART 125-4 RP Select-B Sorbent C18 column using a mixture of methanol and 2% phosphoric acid (pH 2.7) (70:30, v/v) for the mobile phase with a flow injection of 1mL/min. The run time was 4min. Volunteers had saliva and blood sampled before, 1, 2, 3, 4, 5, 6, 8, 11, 24, 48 and 72h after taking a 20mg oral dose of piroxicam. The pharmacokinetic parameters of piroxicam in plasma samples were as follows: AUC0-72 (64819hng/mL), predicted clearance (0.2L/h), distribution volume (14.8L), elimination half-life (50.7h) and saliva/plasma concentration ratio (0.003). The estimation of all pharmacokinetic parameters for 5'-hydroxypiroxicam would require collections beyond 72h; however, it was possible to quantify the mean maximum concentration (133ng/mL), time to peak concentration (53.6h), mean AUC0-72 (6213hng/mL), predicted clearance (110.3L/h) and saliva/plasma concentration ratio (0.04). The developed methods proved effective and sensitive for determining the lower quantification limit of piroxicam in plasma (6.1ng/mL) and saliva (0.15ng/mL) and of 5'-hydroxypiroxicam in plasma (1.2ng/mL) and saliva (0.15ng/mL).

Effective method for the detection of piroxicam in human plasma using HPLC

Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used by the general population to alleviate inflammation and pain after oral surgeries. Piroxicam is among the most commonly used NSAIDs and excels in controlling pain, swelling, trismus and other common symptoms of inflammation. This study aimed to evaluate different concentrations of piroxicam and its major metabolite, 5'-hydroxypiroxicam, in human plasma samples over time using high performance liquid chromatography (HPLC) after liquid-liquid extraction. Briefly, 10 volunteers participated in this study after approval by the Ethics Committee of Bauru School of Dentistry, Universidade de São Paulo - USP, Brazil. Volunteers received a single dose oral of piroxicam (20 mg) and had blood collected at various times following an established protocol. The methodology of liquid-liquid extraction was effective for determining concentrations of piroxicam in plasma using HPLC in 10 out of 10 volunteers while 5'-hydroxypiroxicam was only detected in 2 out of 10 volunteers.

Effects of passive smoke inhalation on the vocal cords of rats.

UNLABELLED: Few studies have demonstrated the pathologic reactions yielded by smoke inhalation on the airway in rats. AIM: The aim of this study was to analyze the possible histopathological effects produced by chronic cigarette smoke inhalation on the vocal folds of rats. STUDY DESIGN: Experimental. MATERIAL AND METHOD: 36 male rats (Rattus norvergicus Wistar strain), aged 60 days, were kept in cages and exposed to inhalation of the smoke produced by 10 cigarettes lit 3 times a day, 7 days a week, for periods of 25, 50 and 75 days, and their respective controls. Thereafter the animals were killed and their larynxes were dissected and submitted to histological processing for achievement of histological sections, which were stained with Hematoxylin and Eosin and analyzed by light microscopy. RESULTS: The rats exposed to smoke displayed smaller (p< 0,05) body mass than the control group. There was hyperplasia and squamous metaplasia in the free edge of the vocal fold and squamous hyperplasia on the middle portion of the vocal fold in all 3 study periods. Moreover, the 50-day group revealed keratinizing metaplasia in this area. Morphological alterations in other areas of the larynx and inflammatory reaction of the lamina propria were also not observed. CONCLUSION: It was concluded that the passive inhalation of cigarette smoke yields important morphological changes in the vocal fold epithelium, which may progress to neoplasia.

Efeitos da inalação passiva da fumaça de cigarro sobre as pregas vocais de ratos / Effects of passive smoke inhalation on the vocal cords of rats

Poucos estudos demonstram as reações patológicas devidas à inalação de fumaça pelas vias aéreas de ratos. OBJETIVO: Estudar e analisar os possíveis efeitos histopatologicos produzidos pela inalação crônica de fumaça de cigarro nas pregas vocais de ratos. DESENHO DE ESTUDO: Experimental. MATERIAL E MÉTODOS: 36 ratos masculinos (Rattus norvergicus Wistar), de 60 dias de idade, foram mantidos em gaiolas e expostos à inalação da fumaça produzida por 10 cigarros, 3 vezes ao dia, 7 dias por semana, para períodos de 25, 50 e 75 dias, e os controles respectivos. Os animais foram sacrificados e as suas laringes dissecadas e submetidas a análise histológica com coloração de Hematoxilina e Eosina e analisados através de microscopia simples. RESULTADOS: Os ratos expostos ao cigarro exibiram menor (p <0,05) massa corporal que o grupo controle. Havia hiperplasia e metaplasia escamosa na extremidade livre da prega vocal e hiperplasia escamosa na porção mediana da prega vocal em todos os 3 períodos de estudo. Além disso, o grupo de 50 dias revelou metaplasia com queratinização nesta área. Não foram observadas alterações morfológicas em outras áreas da laringe e reação inflamatória da lâmina propria. CONCLUSÃO: Foi concluído que a inalação passiva de fumaça de cigarro rende mudanças morfológicas importantes no epitélio da prega vocal que podem, eventualmente, progredir para neoplasia.

Efeito da inalação de carbonato de cálcio nas pregas vocais de ratos / The effect of calcium carbonate inhalation on rats' vocal folds

Tema: efeito da inalação de carbonato de cálcio (principal componente do giz) nas pregas vocais de ratos. Objetivo: verificar em animais o efeito independente da inalação crônica de carbonato de cálcio (CaCO3) nas pregas vocais. Método: foram utilizados 30 ratos divididos em 2 grupos: animais expostos ao CaCO3 e animais mantidos como controle. Após 15, 30 e 90 dias os animais foram sacrificados e as pregas vocais analisadas ao microscópio óptico. Resultados: os resultados demonstraram uma maior concentração de macrófagos vacuolizados no grupo dos animais expostos ao CaCO3. Conclusão: estes resultados sugerem que a inalação crônica de partículas como o CaCO3, consideradas inócuas, pode influenciar o adequado funcionamento das pregas vocais, pois induzem uma maior migração de células de defesa para esta região.

Modificaçöes na atividade de fosfotirosina proteína fosfatase e fosfatase acída em glândula sublingual e fígado de ratos expostos à fumaça de cigarro / Effect of cigarette smoke on sublingual gland liver phosphotyrosine protein phosphatase and acid phosphatase activities

O fumo voluntário e involuntário influencia a saúde geral. Têm-se sugerido ligaçöes entre o hábito de fumar dos pais e a experiência de cáries em crianças. Estudos recentes demonstraram um aumento do estresse oxidativo em diversos tecidos de indivíduos expostos à fumaça do cigarro (FC). Neste trabalho analisamos o efeito da FC na atividade específica da fosfatase ácida total (FAT), fosfatase ácida inespecífica (FAI) e proteinas tirosina fosfatase (PTP) em diversos tecidos de ratos expostos à FC ambiental. Foram utilizados 49 ratos Wistar (Rattus novergicus) machos adultos (200g), divididos aleatoriamente em grupo controle (näo exposto à FC) e experimental. O grupo experimental foi exposto 3 vezes ao dia à fumaça produzida por 10 cigarros (1 cigarro: alcaträo=11mg; nicotina=0,9mg; monóxido de carbono=12mg), durante 10 minutos. Os animais foram sacrificados após 0, 25, 50 e 75 dias. A atividade fosfatásica (nmol/min mg) foi determinada no extrato solúvel dos tecidos analisados, utilizando 5 mM de pNPP como substrato no pH 5 e 37ºC. Na glândula sublingual ocorreu um aumento de cerca de 2x na FAT e FAI e 3,5 vezes na PTP após 25 dias; após 50 dias a atividade FAT e PTP foi menor que 50 por cento em relaçäo ao grupo controle, mantendo-se neste patamar após 75 dias. No fígado, após 25 dias, ocorreu um aumento de cerca de 500 por cento na FAT, PTP e FAI; após 50 dias houve marcante diminuiçäo (75 por cento) na atividade dessas enzimas. A sensibilidade das diferentes isoformas da fosfatase ácida à FC a coloca como potencial biomarcador das alteraçöes induzidas pela exposiçäo à fumaça de cigarro ambiental. Concluímos que a exposiçäo crônica à FC promove marcante diminuiçäo da atividade fosfatase ácida e PTP na glândula salivar sublingual e no fígado de ratos. A inibiçäo da PTP poderia ser o início de modificaçöes moleculares relacionadas a algumas doenças associadas ao cigarro uma vez que essa classe de enzimas desempenha papel fundamental no controle da proliferaçäo, crescimento e diferenciaçäo celular

Farmacologia dos anestésicos locais: consideraçöes gerais / Pharmacology of the local anesthetics: general considerations

No presente trabalho faz-se uma recapitulaçäo do histórico da anestesia para poder-se situar a contribuiçäo da Odontologia à Saúde, avaliando-se detalhadamente a farmacologia dos anestésicos locais utilizados em Odontologia, além de uma referência à história da anestesia e dos anestésicos locais para uma situaçäo do tempo de suas descobertas. Säo apresentadas de maneira clara e objetiva as vias sensoriais e o trajeto da sensaçäo da dor. As propriedades desejáveis dos anestésicos locais também säo discutidas em apropriado nível de conhecimento. Será também apresentada a relaçäo da estrutura química e da atividade farmacológica dos anestésicos. O mecanismo de açäo das drogas anestésicas será mostrado de maneira sucinta e objetiva. A sensibilidade diferencial das fibras nervosas também é analisada. Destaque todo especial é também feito sobre a influência do pH no efeito do anestésico local, assim como da associaçäo dos vasoconstritores. As açöes farmacológicas säo também discutidas, além do metabolismo e excreçäo. Finalmente, säo analisadas as substâncias anestésicas tipo amidas, tais como a lidocaína, a bupivacaína, a mepivacaína e a prilocaína

Mecanismos biológicos e influência de fatores ambientais na fluorose dentária e a participaçäo do flúor na prevençäo da cárie: revisäo de literatura / Biological mechanisms and influence of environmental factors in the dental fluorosis. The role of fluoride in the caries prevention: a literature review

O flúor tem uma importante participaçäo na prevençäo da cárie dentária, estando disponível principalmente na água de abastecimento. Este íon tem sido associado com a inibiçäo da desmineralizaçäo e a aceleraçäo da remineralizaçäo durante o processo carioso. A presença constante do flúor nos fluídos bucais constitui o principal fator na prevençäo da cárie. Além disso, tem-se demonstrado que o flúor na placa bacteriana pode inibir a produçäo de ácidos pelas bactérias cariogênicas. Entretanto, fluorose dentária pode ocorrer se as concentraçöes de flúor forem excessivas no interior ou nas proximidades do esmalte em formaçäo, durante sua fase de desenvolvimento pré-eruptiva. A fluorose caracteriza-se pelo aumento da porosidade na superfície e subsuperfície do esmalte, resultando em esmalte com aparência opaca. Os efeitos tóxicos do flúor sobre o esmalte em desenvolvimento estäo associados com sua influência tanto sobre os ameloblastos, como sobre o estágio de maturaçäo da formaçäo do esmalte. No momento da prescriçäo de terapia com flúor, os profissionais devem ter conhecimento da exposiçäo total do paciente ao flúor, bem como dos fatores ambientais que podem influenciar a sua absorçäo e aumentar a incidência e gravidade da fluorose dentária. O objetivo desta revisäo é discutir os mecanismos biológicos e a influência dos fatores ambientais na fluorose dentária. A participaçäo do flúor na prevençäo da cárie também será discutida, abordando a desmineralizaçäo e remineralizaçäo dentária e seu efeito inibitório sobre a placa bacteriana