Interaction between physical exercise and APOE gene polymorphism on cognitive function in older people

We aimed to present an overview of the literature regarding the interaction between physical exercise and APOE gene polymorphism on cognitive function, particularly in patients with Alzheimer's disease (AD). Firstly, this review focused on the effect of the physical exercise on cognitive function, regardless of APOE gene polymorphism. Some studies have shown that a high level of cardiorespiratory fitness is associated with less neuronal damage with an improvement in memory score tests whereas other studies failed to detect any association between physical exercise and cognitive improvement either in healthy individuals or patients with AD. Taken together, standardized protocols and more longitudinal studies are required to provide a better insight into the effects of physical exercise on cognitive function. Although there is no agreement in the literature regarding the effects of physical exercise on cognitive function, it is well established that it improves social interaction and the feeling of well-being, thereby positively contributing to the quality of life of the elderly. Regarding the influence of physical exercise on cognitive function in APOE ε4 allele carriers, the data trend shows that the carriers of allele ε4 for APOE gene were more responsive to the beneficial effects of physical exercise on cognitive function compared with non-carriers. Nevertheless, studies with larger sample sizes will provide more accuracy about this relationship.

Interaction between physical exercise and APOE gene polymorphism on cognitive function in older people.

We aimed to present an overview of the literature regarding the interaction between physical exercise and APOE gene polymorphism on cognitive function, particularly in patients with Alzheimer's disease (AD). Firstly, this review focused on the effect of the physical exercise on cognitive function, regardless of APOE gene polymorphism. Some studies have shown that a high level of cardiorespiratory fitness is associated with less neuronal damage with an improvement in memory score tests whereas other studies failed to detect any association between physical exercise and cognitive improvement either in healthy individuals or patients with AD. Taken together, standardized protocols and more longitudinal studies are required to provide a better insight into the effects of physical exercise on cognitive function. Although there is no agreement in the literature regarding the effects of physical exercise on cognitive function, it is well established that it improves social interaction and the feeling of well-being, thereby positively contributing to the quality of life of the elderly. Regarding the influence of physical exercise on cognitive function in APOE ε4 allele carriers, the data trend shows that the carriers of allele ε4 for APOE gene were more responsive to the beneficial effects of physical exercise on cognitive function compared with non-carriers. Nevertheless, studies with larger sample sizes will provide more accuracy about this relationship.

Simultaneous determination of dextromethorphan, dextrorphan and doxylamine in human plasma by HPLC coupled to electrospray ionization tandem mass spectrometry: application to a pharmacokinetic study.

In the present study, a fast, sensitive and robust method to quantify dextromethorphan, dextrorphan and doxylamine in human plasma using deuterated internal standards (IS) is described. The analytes and the IS were extracted from plasma by a liquid-liquid extraction (LLE) using diethyl-ether/hexane (80/20, v/v). Extracted samples were analyzed by high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Chromatographic separation was performed by pumping the mobile phase (acetonitrile/water/formic acid (90/9/1, v/v/v) during 4.0min at a flow-rate of 1.5 mL min⁻¹ into a Phenomenex Gemini® C18, 5 µm analytical column (150 × 4.6 mm i.d.). The calibration curve was linear over the range from 0.2 to 200 ng mL⁻¹ for dextromethorphan and doxylamine and 0.05 to 10 ng mL⁻¹ for dextrorphan. The intra-batch precision and accuracy (%CV) of the method ranged from 2.5 to 9.5%, and 88.9 to 105.1%, respectively. Method inter-batch precision (%CV) and accuracy ranged from 6.7 to 10.3%, and 92.2 to 107.1%, respectively. The run-time was for 4 min. The analytical procedure herein described was used to assess the pharmacokinetics of dextromethorphan, dextrorphan and doxylamine in healthy volunteers after a single oral dose of a formulation containing 30 mg of dextromethorphan hydrobromide and 12.5mg of doxylamine succinate. The method has high sensitivity, specificity and allows high throughput analysis required for a pharmacokinetic study.

Comparative bioavailability of two escitalopram formulations in healthy human volunteers.

OBJECTIVE: To assess the bioequivalence of two escitalopram formulations (Test formulation: escitalopram (10 mg tablet) manufactured by Apsen Farmacêutica S.A.) Reference formulation: escitalopram (Lexapro; 10 mg tablet) from Lundbeck Brasil Ltda) in healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, two-period crossover design with at least a 21-day washout interval. Plasma samples were obtained over a 168 h period. Plasma escitalopram concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). The following pharmacokinetic parameters were obtained from the escitalopram plasma concentration vs. time curves: AUC(last), AUC(inf) and C(max). RESULTS: The limit of quantification for escitalopram was 0.2 ng x ml(-1). The geometric mean with corresponding 90% confidence interval (CI) for Test/Reference percent ratios were 97.35% (90% CI = 90.28-104.96%) for C(max), 99.60% (90% CI = 92.93-106.74%) for AUC(last) and 99.92% (90% CI = 93.34-106.97%) for AUC(inf). CONCLUSION: Since the 90% CI for AUClast, AUCinf and Cmax ratios were within the 80-125% interval proposed by the US FDA, it was concluded that escitalopram formulation manufactured by Apsen Farmacêutica S.A. is bioequivalent to the Lexapro formulation in regard to both the rate and the extent of absorption.

Comparative bioavailability of three ibuprofen formulations in healthy human volunteers.

OBJECTIVE: To assess the bioequivalence of three ibuprofen formulations (Test formulation: ibuprofen (400 mg capsule) manufactured by Cardinal Health Brasil 402 Ltda. (Sorocaba, Brazil) and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. (SA poundo Paulo, Brazil); Reference formulation (1): ibuprofen (AdvilA(R); 2 A 200 mg coated tablet) from Wyeth-Whitehall Ltda. (Itapevi, Brazil); Reference formulation (2): ibuprofen (AliviumA; 8 ml A 50 mg/ml solution) from Schering Plough S.A. (Rio de Janeiro, Brazil)) in 24 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, three-period crossover design with at least 5-day washout interval. Plasma samples were obtained over a 24-h period. Plasma ibuprofen concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). The following pharmacokinetic parameters were obtained from the ibuprofen plasma concentration vs. time curves: AUC(last), AUC(trunctmax), AUC(inf) and C(max). RESULTS: The limit of quantification for ibuprofen was 0.1 microg A ml(1). The geometric mean with corresponding 90% confidence interval (CI) for Test/Reference (1) percent ratios were 114.24% (90% CI = 105.67, 123.50%) for C(max), 98.97% (90% CI = 94.69, 103.44%) for AUC(last) and 99.40% (90% CI = 95.21, 103.78%) for AUC(inf). The geometric mean and respective 90% confidence interval (CI) for Test/Reference (2) percent ratios were 108.38% (90% CI = 100.19, 117.25%) for C(max), 100.79% (90% CI = 96.39, 105.40%) for AUC(last) and 101.26% (90% CI = 96.94, 105.77%) for AUC(inf); t(max) for the 400 mg Test capsule was shorter than that for the 2 A 200 mg Reference (1) tablets (p < 0.002). CONCLUSION: Since the 90% CI for AUC(last), AUC(inf) and Cmax ratios were within the 80 - 125% interval proposed by the US FDA, it was concluded that ibuprofen formulation manufactured by Cardinal Health Brasil 402 Ltda. and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. is bioequivalent to the AdvilA and AliviumA formulations with regard to both the rate and the extent of absorption.

A bioequivalence study of gliclazide based on quantification by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry.

OBJECTIVE: The aim of this study was to evaluate, in human volunteers, the performance of one gliclazide tablet formulation (gliclazide 80 mg tablet from EMS Indústria Farmacêutica Ltda.) against two reference gliclazide tablet formulations (Diamicron 80 mg tablet from Servier do Brazil Ltda. and Diamicron 80 mg tablet from Servier (Ireland) Industries Limited). METHODS: The study had an open, randomized, three-period crossover design with a one-week washout interval between doses. The samples were obtained over a 48-h interval after each oral administration of gliclazide. The samples were extracted from plasma using diethylether : hexane (80 : 20, v/v) and the extracts were analyzed by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/ MS). Chromatography was performed isocratically using a Jones Chromatography Genesis C8 120A 4u. The method had a chromatographic run-time of 2.5 min and a calibration curve of the range of 0.02- 10 microg x ml(-1) (r(2) > 0.9993). The limit of quantification was 0.02 microg x ml(-1). RESULTS: The geometric mean and 90% confidence intervals (CI) for the Gliclazide/Diamicron (Ireland) ratio were 588.68% (90% CI= 491.16, 705.58%) for AUClast, 423.50% (90% CI = 338.25, 530.23%) for AUCinf, and 1395.77% (90% CI= 1116.62, 1744.72%) for Cmax. The geometric mean and 90% confidence intervals (CI) for the Gliclazide/Diamicron (Brazil) ratio were 249.16% (90% CI = 207.96, 298.54%) for AUCiast, 249.16% (90% CI = 207.96 - 298.54%) for AUCinf, and 188.04% (90% CI - 151.72, 233.05%) for Cmax. CONCLUSION: Since the 90% CI for Cmax, AUClast and AUC(0-infinity) ratios were all outside the 125% interval proposed by the US Food and Drug Administration, we concluded that the gliclazide test formulation were not bioequivalent to either reference formulation. Interestingly, the pharmacokinetic parameters such as Cmax, AUClast of both reference formulations are compatible with neither the literature nor the profile of an immediate release formulation. In addition, both reference formulations were not bioequivalent in themselves, indicating significant differences in reference product formulation.

Cyclosporine bioequivalence study: quantification using fluorescence polarization immunoassay (FPIA) and radioimmunoassay (RIA).

OBJECTIVE: The aim of study was to compare the bioavailability of 2 cyclosporine capsule formulations (100 mg; Sigmasporin Microoral from Novaquímica Divisão Nature's Plus Farmacêutica Ltd., Brazil, as test formulation and Sandimmune Neoral from Novartis Biociências S.A., Brazil, as reference formulation) in 24 healthy male volunteers. METHODS: The study was open, randomized, with a 2-period crossover, a 1-week washout interval between doses. Blood samples were obtained over a 12-hour interval after each oral administration of cyclosporine (2 capsules of 100 mg of each formulation). Cyclosporine blood concentrations were quantified using a fluorescence polarization immunoassay (FPIA) method provided by Abbott Axsym System and Cyclo-Trac SP. Whole-blood radioimmuoassay (RIA) kit was provided by DiaSorin. These assays provided concentration-time curves for cyclosporine in blood concentration from which the following pharmacokinetic parameters were obtained: AUC(last), AUC(inf), Cmax. RESULTS: Geometric mean and 90% confidence intervals (CI) of Microoral/Neoral as percent ratios were 94.5% (90.8-98.4%) for AUC(last), 93.8% (89.7-98.1%) for AUC(inf), and 98.1% (94.5-101.8%) for Cmax when cyclosporine was determined using FPIA and 96.1% (91.9 to 100.6%) for AUC(last), 95.2% (90.2-100.5%) for AUC(inf), and 99.4% (96.4-102.4%) for Cmax using RIA. CONCLUSION: Since the 90% CI for Cmax, AUC(last) and AUC(inf) ratio were within the 80-125% interval proposed by US-FDA, it is concluded that Sigmasporin Microoral 100 mg capsule formulation is bioequivalent to Sandimmune Neoral 100 mg capsule formulation with regard to both rate and the extent of absorption.

Bioequivalence study of two fluconazole capsule formulations in healthy volunteers.

OBJECTIVE: To compare the bioavailability of a fluconazole 150 mg capsule formulation from Laboratório Teuto Brasileiro Ltd., Brazil (test formulation), and Zoltec 150 mg capsule from Laboratórios Pfizer Ltd., Brazil (reference formulation), in 24 volunteers of both sexes. MATERIAL AND METHODS: The study was conducted open with randomized 2-period crossover design and a 2-week washout period. Plasma samples were obtained over a 168-hour interval. Fluconazole concentrations were analyzed by combined reversed-phase liquid chromatography and tandem mass spectrometry (LC/MS/MS) with positive ion electrospray ionization using selected ion monitoring method. From the fluconazole plasma concentration vs. time curves the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-inf) and C(max). RESULTS: Geometric mean of fluconazole/Zoltec 150 mg individual percent ratio was 102.6% for AUC(last), 102.2% for AUC(0-inf) and 109.4% for C(max). The 90% confidence intervals were 97.3-108.2%, 97.0-107.8%, and 103.1-116.0%, respectively. CONCLUSION: Since the 90% CI for both Cmax, AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that fluconazole 150 mg capsule was bioequivalent to Zoltec 150 mg, according to both the rate and extent of absorption.

Amlodipine bioequivalence study: quantification by liquid chromatography coupled to tandem mass spectrometry.

OBJECTIVE: To assess the bioequivalence of two amlodipine tablet formulations (Amlodipine 5 mg tablet from Merck S.A. Indústrias Químicas, Brazil as test formulation and Norvasc 5 mg tablet from Laboratórios Pfizer Ltd., Brazil as reference formulation) in 24 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized two-period crossover design with a 4-week washout interval. Plasma samples were obtained over a 144 h period. Plasma amlodipine concentrations were analyzed by combined liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the amlodipine plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-inf) and C(max). The statistical interval proposed was 80-125% according to the US Food and Drug Administration Agency. RESULTS: The limit of quantification was 0.1 ng/ml for plasma amlodipine analysis. The geometric mean and the 90% confidence interval (CI) test/reference ratios were 101.2 (92.9-110.2%) for AUC(last), 99.6 (91.5-108.4%) for AUC(0-inf) and 98.5 (89.0-109.1%) for C(max). CONCLUSION: Since the 90% CI for AUC(last), AUC(0-inf) and C(max) ratios were within in the 80-125% interval proposed by the US FDA, it was concluded that Amlodipine 5 mg tablet (test formulation) was bioequivalent to Norvasc 5 mg tablet, in terms of both rate and extent of absorption.

Relações endo-perio: lesão endodôntica primária / Endo-perio relationship: primary endodontic lesion

Os autores relatam a cura clínica de uma lesão do ligamento periodontal, ao nível da furcação, após o tratamento endodôntico e chamam a atenção para o fato de que a existência de canais ao nível do assoalho da câmara pulpar exige que o tratamento endodôntico, nos dentes multirradiculares, seja concluído pela repleção hermética dos canais radiculares e da câmara pulpar