Assessment of remineralization potential of Theobromine and Sodium Fluoride gels on Artificial Caries like lesions / Avaliação do potencial de remineralização de géis de teobromina e fluoreto de sódio em lesões de cárie artificial

Objective: To compare the remineralization potential of theobromine and sodium fluoride gels on artificial caries like lesion. Materials and Methods: Forty longitudinal halves of human mandibular premolars were equally divided into 4 groups of 10 samples each: control group (C), samples were stored in distilled water during the experiment period. The remaining 30 specimens were subjected to demineralization protocol to create caries like lesions. samples were immersed for three days in a demineralization solution (pH 5.0) containing 0.2% carbopol and 0.1% lactic acid saturated with calcium phosphate tribasic. The samples were subdivided into 3 equal groups according to the treatment applied during the pH cycle. Demineralization group "D": no treatment applied. Group "F" treated with 2000 mg/liter sodium fluoride gel. Group "T" treated with 200 mg/liter theobromine gel. The specimens of the two studies groups were subjected to Demineralization- Remineralization PH Cycle Protocol for 5 days (Alternating four steps: 1: Treatment material, fluoride or theobromine ˜= 3 minutes. 2: Demineralizing solution 3 hours. 3: treatment material ˜= 3 minutes. 4: Remineralizing solution till the next cycle). The samples were investigated by scanning electron microscope (SEM) and energy dispersive x-ray analysis (EDXA). Results: The enamel of the demineralization group was porous with artificial caries like changes exposing the subsurface enamel rods with severe rod core defects. Theobromine gel and fluoride gel groups showed marked improvement in the surface characteristics in the enamel in both groups. Theobromine gel group showed more observable enamel surface improvement than the fluoride gel group. EDXA revealed that the calcium-phosphorus ratio displayed a descending order: (C > T > F > D). The differences between the two tested groups were not statistically significant. Conclusion: Theobromine gel had more effective remineralizing potential than fluoride gel as a result of its effect in improving the enamel surface characteristics of human teeth. (AU)

Objetivo: Comparar o potencial de remineralização dos géis de teobromina e fluoreto de sódio em lesões de cáries artificiais. Materiais e Métodos: Quarenta metades longitudinais de pré-molares inferiores humanos foram igualmente divididas em 4 grupos de 10 amostras cada: grupo controle (C), as amostras foram armazenadas em água destilada durante o período do experimento. As 30 amostras restantes foram submetidas ao protocolo de desmineralização paracriar lesões artificiais de cárie. As amostras foram imersas por três dias em uma solução de desmineralização (pH 5,0) contendo 0,2% de carbopol e 0,1% de ácido lático saturado com fosfato de cálcio tribásico. As amostras foram subdivididas em 3 grupos iguais, de acordo com o tratamento aplicado durante o ciclo do pH. Grupo de desmineralização "D": nenhum tratamento aplicado. Grupo "F" tratado com 2000 mg / litro de fluoreto de sódio em gel. Grupo & quot;T &q uot; tratado com 200 mg / litro de gel de teobromina. As amostras dos dois grupos de estudo foram submetidas ao protocolo de ciclo de desmineralização - remineralização por 5 dias (quatro etapas alternativas: 1: material de tratamento, flúor ou teobromina ˜= 3 minutos. 2: solução desmineralizante 3 horas. 3: material de tratamento ˜= 3 minutos 4: Solução de remineralização até o próximo ciclo). As amostras foram investigadas por microscopia eletrônica de varredura(MEV) e análise de raios-x dispersivos de energia (EDXA). Resultados: O esmalte do grupo de desmineralização era poroso, com cáries artificiais, como alterações que expunham as hastes de esmalte do subsolo com graves defeitos no núcleo da haste. Os grupos gel de teobromina e flúor apresentaram melhora acentuada nas características da superfície do esmalte nos dois grupos. O grupo gel de teobromina mostrou uma melhoria na superfície do esmalte mais observável do que o grupo gel de fluoreto. A EDXA revelou que a razão cálcio-fósforo exibia uma ordem decrescente: (C> T> F> D). As diferenças entre os dois grupos testados não foram estatisticamente significantes. Conclusão: O gel de teobromina teve um potencial remineralizante mais eficaz que o gel de flúor como resultado de seu efeito na melhoria das características da superfície do esmalte dos dentes humanos. (AU)

Pharmacokinetic Interaction of Chrysin with Caffeine in Rats

Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism.

Effects of Baicalin on Oral Pharmacokinetics of Caffeine in Rats

Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated IC50 values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats.

Efficacy and Tolerability of Theobromine in Patients with Upper Airway Cough Syndrome: A Multicenter, Double-Blind, Randomized, Active Drug Comparative Study

OBJECTIVES: The objective of this study is to evaluate the efficacy and tolerability of theobromine in patients with upper airway cough syndrome compared to those of levocloperastine. MATERIALS AND METHOD: This was a randomized, double-blind study. One hundred sixty-five patients with upper airway cough syndrome participated in a 5 day treatment; 85 subjects were included in the theobromine treatment group and 80 in the levocloperastine control group. Cough severity score, daytime cough symptom (DCS), nighttime cough symptom (NCS) and cough quality of life questionnaire (CQLQ) were analyzed for symptom analysis, and vital signs and laboratory study were performed for safety evaluation before and after medication administration. RESULTS: The primary efficacy analysis showed that the mean change in cough grade between baseline and follow-up in the treatment group was lower than that in the control group. This led to the conclusion that theobromine has similar efficacy to control treatment. The secondary efficacy analysis of changes in DCS, NCS and CQLQ verified this conclusion. Considering safety, only one case of dyspepsia was considered to be probably related to theobromine. Other tests conducted before and after treatment confirmed the safety of treatment medications. CONCLUSION: Theobromine is a novel natural antitussive medication that has similar efficacy to levocloperastine and adequate safety.

Action of AMP579 and adenosine on potassium or sodium ionic channels in isolated rat and guinea pig ventricular myocytes / 药学学报

<p><b>AIM</b>To study the effect of AMP579 and adenosine on potassium ionic (K+) or sodium ionic (Na+) channels and to elucidate ionic mechanisms underlying negative inotropic and antiarrhythmic effects of AMP579 and adenosine.</p><p><b>METHODS</b>Ionic channel currents of rat and guinea pig ventricular myocytes were recorded by patch clamp technique in whole-cell configuration.</p><p><b>RESULTS</b>Adenosine showed a stronger activating effect on transient outward K+ current (I(to)) than AMP579, EC50 of adenosine and AMP579 were 2.33 and 8. 32 micromol x L(-1), respectively (P < 0.05). An adenosine A1 receptor blocker, 1,3-dipropyl-8-cyclopentylxanthine (PD116948), can abolish the effects of AMP579 and adenosine on I(to), demonstrating that the effect is mediated by adenosine A1 receptor. Adenosine exerted a more obvious inhibitory effect on delayed rectifier K+ current (IK) than AMP579. IC50 of adenosine and AMP579 were 1.21 and 2.31 micromol x L(-1), respectively (P < 0.05). AMP579 had a more powerful inhibitory effect on inward rectifier K+ current (IK1) than adenosine. IC50 of AMP579 and adenosine were 4.15 and 20.7 micromol x L(-1), repectively (P < 0.01). AMP579 and adenosine exerted a similar inhibitory effect on fast inward Na+ current (INA), IC50 of AMP579 and adenosine were 9.46 and 6.23 micromol x L(-1), respectively (P > 0.05).</p><p><b>CONCLUSION</b>Adenosine showed a stronger activating effect on I(to) than AMP579, however, the mechanism of AMP579 and adenosine activating I(to) was mediated by adenosine A1 receptor. AMP579 has a more powerful inhibitory effect on IK1, and less inhibitory effect on IK than adenosine. Both drugs have a similar inhibitory effect on INa. The negative inotropic and antiarrhythmic effects are related to these ionic mechanisms.</p>

Achocolatados: análise química / Chocolate drink powders: chemical analysis

Neste trabalho avaliaram-se propriedades químicas de achocolatados do mercado brasileiro, sendo estas os teores de lipídios, proteínas, cinzas, umidade, pH, teobromina e alcalóides totais. Estas propriedades são influenciadas principalmente pelo conteúdo dos ingredientes lácteos, como o leite em pó e o soro de leite em pó. Foi feito um comparativo entre as marcas de achocolatados, dando ênfase às grandes diferenças, quando existentes, entre os achocolatados dietéticos (para dietas de restrição de sacarose, frutose e glicose (dextrose) e ®light¼ (com redução de açúcares) e os tradicionais

Determinação silmutânea de teobromina, teofilina e cafeína em chás por cromatografia líquida de alta eficiência / Simultaneous determination of the theobromine, theophylline and caffeine in teas by high permonance liquid chromatography

Para a realização deste trabalho, foram analisadas 10 amostras de diferentes tipos e marcas de chás com o objetivo de se quantificar teobromina, teofilina e cafeína silmultaneamente. Para tanto, otimizou-se técnica de cromatografia líquida de alta eficiência (CLAE) baseada na ISO 10095(1992), utilizando-se coluna Inertsil ODS-3 (150x4 mm, 5µm), fase móvel de ácido acético 1 por cento + acetonitrila (95:5, v/v), fluxo 1 mL/min e detector de UV/VIS ajustado em 273nm. Os resultados de cafeína obtidos por esse método foram comparados com os obtidos por um método espectrofotométrico de acordo com Schormüller (1970)...

Methylxanthines of Ilex paraguariensis A. St.-Hil. var. vestila Loes. and var. paraguariensis

Methylxanthine contents of maté (Ilex paraguariensis A. St.-Hil.) plants of two varieties (vestita Loes. and paraguariensis) are reported. The plants were cultivated in Ivaí, Paraná, southern Brazil (20º 00' S 50º 50' W), and leaves were gathered in two different harvest times: October, 1998, and February, 2000. Methylxanthine content was found higher in February, 2000, for the two varieties. The var. vestita exhibited lower caffeine contents than the var. paraguariensis in both harvest times. No differences on the theobromine contents between the two varieties were found. The developed HPLC method showed reliable resolution to theobromine, an important feature since we observed some plants with higher theobromine...

Assessment of flavin-containing monooxygenase (FMO) activity by determining urinary ratio of theobromine and caffeine in a Korean population after drinking a cup of coffee

To examine individual variation in drug metabolism catalyzed by flavin-containing monooxygenase (FMO), 179 Korean volunteers' urinary molar concentration ratio of theobromine (TB) and caffeine (CA) was determined. Their urine was collected for 1 hr (between 4 and 5 hrs) after they drank a cup of coffee containing 115 mg CA and analyzed by an HPLC system. The lowest TB/CA ratio obtained was 0.40, the highest ratio was 15.17 (38-fold difference), and the median ratio for all subjects was 1.87. The mean was 2.66 with 2.36 S.D.. In 134 nonsmokers, the mean ratio was 2.35 +/- 1.93, that of 51 males was 2.30 +/- 2.26 and 83 females was 2.37 +/- 1.85, respectively. There was no significant gender difference in the obtained TB/CA ratio (Mann-Whitney test; p=0.518). There were no smokers among the 83 female volunteers. In the remaining 96 male subjects, the ratio obtained in 51 nonsmokers was 2.30 +/- 2.06 and that of 45 smokers was 3.62 +/- 3.19. This indicated that the TB/CA ratio was increased significantly in smokers (p=0.007). However, when the TB/CA ratios (FMO activity) obtained in all 179 Korean volunteers are compared with the urinary concentration ratios of paraxanthine (PX) plus 1,7-dimethylurate (17U) to CA (CYP1A2 activity), there was a weak but significant correlation (Pearson's correlation coefficient test; r2=0.28, p<0.0001). This indicates that, although the urinary TB/CA ratio mostly represents FMO activity, minor contribution by CYP1A2 activity cannot be ignored. In conclusion, the FMO activity measured by taking the urinary TB/CA ratio from normal healthy Korean volunteers shows marked individual variations without significant gender differences and the increased TB/CA ratio observed in cigarette smokers may have been caused by the increased CYP1A2 activity.

Determinaçäo de teobromina e cafeína em cacau e produtos de chocolate pro cromatografia líquida de alta eficiência / High pressure liquid chromatographic determination of theobromine and caffeine in cocoa and chocolate products

Com o objetivo de determinar os teores de teobromina e cafeína, 77 amostras de produtos de chocolate foram analisadas. As amostras testadas foram 12 amostras de massa de cacau, 4 amostras de aroma de cacau e 61 amostras de alimentos à base de cacau, tais como barras de chocolate, bebidas lácteas, biscoitos, bolos, sorvetes, etc. de diferentes marcas. O método utiliza a técnica de cromatografia líquida de alta eficiência, com detector de arranjo de diodos, coluna C18 e fase móvel metanol - água - ácido acético (20:79:1). A quantificaçäo foi feita por padronizaçäo externa

Identificacao cromatografica de cafeina ,teofilina, teobromina e paraxantina em amostras de urina / Chromatographic identification of caffeine, theophylline,theobromine and paraxanthine in urine samples

O Comite Olimpico Internacional propoe medidas para coibir o abuso de cafeina nas atividades esportivas, mas nao faz referencia ao controle de outras metilxantinas estimulantes, como teofilina, teobromina e paraxantina. No presente trabalho foi proposto um metodo para identificar estes farmacos em urina para fins de controle da dopagem. Aliquotas de urina foram submetidas a extracao com cloroformio-isopropanol em meio basico e os extratos analisados por cromatografia em camada delgada e fase gasosa. Na primeira tecnica a separacao foi feita em silicagel G60 com os seguintes sistemas solventes de desenvolvimento: A) acetato de etila-cicloexano-metanol-hidroxido de amonio e acetato de etila-cicloexano-hidroxido de amonio usados sucessivamente e B) cloroformio-acetona-n-butanol-hidroxido de amonio. Foram estabelecidos perfis normais de urina para populacao consumidora de alimentos xantinicos. Para confirmacao de resultados anormais foi utilizada a cromatografia em fase gasosa com detetor de ionizacao de chamas e coluna capilar metilsilicona. A identificacao da cafeina e de produtos de butilacao das dimetilxantinas foi feita pelo indice de retencao de Kovats e retencao relativa

Pentoxifylline--a new drug for the treatment of intermittent claudication.

Pentoxifylline, a xanthine analogue was evaluated for efficacy, safety and tolerance in the treatment of intermittent claudication in a pilot study. Evaluation was performed in 35 cases. 20 patients were given Pentoxifylline in doses of 1200 mg daily, and 15 patients were given placebo for a period of 8 weeks respectively. Pentoxifylline given in doses of 1200 mg was significantly more effective than the placebo in increasing both the initial and absolute claudication distance (ICD & ACD) in patients with chronic occlusive arterial disease. The subjective parameters, such as paraesthesias, muscular cramps and sensation of heaviness in the legs paralleled the course of walking parameters. These results support the hypothesis that Pentoxifylline in doses of 400 mg TDS reduces blood viscosity by improving red cell flexibility, and thereby enhances blood flow in patients with COAD (Fontaine Stage II or Stage III). Pentoxifylline is thus regarded as a promising drug for circulatory ischaemic disorders, especially in intermittent claudication. It was well tolerated with minimal untoward effects.

A monitorizaçäo plasmática das metilxantinas do guaraná e a importancia na agregaçäo plaquetária / The plasma monitoring of methylxanthines of guarana and its importance in platelet aggregation

Num estudo placebo randomizado, 14 voluntários sadios foram tratados durante dois dias com extrato bruto de Guaraná. A suspensäo aquosa foi administrada em doses de 4 e 8g, três vezes ao dia. Após um período de "wash out", seguiu-se o tratamento com placebo, no mesmo esquema anterior. Desenvolveu-se uma técnica de análise simultânea das metilxantinas envolvidas (teofilina, cafeína e teobromina) em cromatografia líquida de alta pressäo após extraçäo conveniente do plasma em meio ácido com solvente orgânico. O método proposto se mostrou sensível, linear, reprodutível, seletivo, específico e portanto adequado à análise destes compostos em plasma após ingestäo do componente terapêutico nas doses de 4 a 8g. A administraçäo do produto aos voluntários evidenciou níveis plasmáticos dose dependentes para as metilxantinas envolvidas. Verificou-se ainda que houve uma correlaçäo linear positiva apenas entre níveis plasmáticos da cafeína e a inibiçäo da agregaçäo plaquetária em sangue total, mas näo em plasma rico em plaquetas. Näo houve correlaçäo entre doses, efeito biológico e níveis plasmáticos das demais metilxantinas ou por estas näo exercem influência digna de nota sobre a agregaçäo plaquetária ou abtençäo de concentraçäo plasmática subterapêutica utilizando aquelas doses

Estimation of theophylline and theobromine in pharmaceutical preparations and natural products

A proposed GLC procedure for the determination of theophylline and theobromine is presented. They were methylated with Methelute and determined as caffeine. The GLC procedure proved to be simpler and more time saving than the spectrophotometric methods without loss of accuracy. The interference of the accompanying ingredients could be eliminated