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OBJECTIVE: The aim of the current study was to assess the association between 3 different calcium channel blockers (CCBs) (nifedipine, amlodipine and felodipine) and gingival overgrowth in patients with a diagnosis of severe refractory hypertension. METHODS: One hundred and sixty-two patients with severe refractory hypertension, taking CCBs, were selected. Gingival overgrowth was graded and periodontal measurements were recorded (probing pocket depth, clinical attachment level, plaque index and bleeding on probing). Unconditional multivariable binary logistic regression analyses were performed to assess the association between CCB intake and gingival overgrowth after adjusting for potential confounders. RESULTS: Of the 162 patients, 26 (16.0%) were current smokers and 101 (62.3%) were females. The mean age (SD) was 54.1 (8.5) years and the median age (range) 52.5 (39-78) years. Gingival overgrowth was observed in 55 patients (34.0%). Nifedipine was the most common medication (35.2%; 57 of 162). The results of multiple binary logistic regression showed statistically significant associations between CCB intake (exposure) and gingival overgrowth (outcome) after adjusting for the variables treatment time with antihypertensive and plaque index. Patients with gingival overgrowth were 2.5 (odds ratio = 2.46; 95% confidence interval: 1.04-5.82) and 4.0 (odds ratio = 3.90; 95% confidence interval: 1.47-10.35) times more likely to be taking nifedipine and amlodipine, respectively, than patients without gingival overgrowth. On the other hand, this significant association was not observed for felodipine. CONCLUSION: Nifedipine and amlodipine, but not felodipine, were associated with gingival overgrowth in patients with severe refractory hypertension.

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OBJECTIVES: to analyze the Pelvic Floor Muscle Strength (PFMS) of pregnant women with one or more vaginal or cesarean deliveries; to compare the PFMS of these with pregnant women with the PFMS of primiparous women. METHODS: cross-sectional study with women up to 12 weeks pregnant, performed in Itapecerica da Serra, São Paulo state, from December 2012 to May 2013. The sample consisted of 110 pregnant women with one or more vaginal deliveries or cesarean sections and 110 primigravidae. The PFMS was evaluated by perineometry (Peritron(tm)) and vaginal digital palpation (modified Oxford scale). RESULTS: the average PFMS in pregnant women with a history of vaginal delivery or cesarean section was 33.4 (SD=21.2) cmH2O. From the Oxford scale, 75.4% of the pregnant women with previous vaginal or cesarean deliveries presented grade ≤ 2, and 5.5% grade ≥ 4; among the primiparae, 39.9% presented grade ≤ 2, and 50.9% grade ≥ 4, with a statistically significant difference (p<0.001). From the perineometry, there was no statistically significant difference between the PFMS and age, type of delivery, parity, body mass index, and genitourinary tract symptoms, however, there was a statistically significant difference between the pregnant women with and without a history of episiotomy (p=0.04). In the palpation, none of the variables showed a statistically significant difference. CONCLUSION: pregnancy and childbirth can reduce the PFMS. .

OBJETIVOS: analisar a força muscular do assoalho pélvico de gestantes com um ou mais partos normais ou cesarianas; comparar a a força muscular do assoalho pélvico dessas gestantes com a de primigestas. MÉTODO: estudo transversal com gestantes até 12 semanas de gravidez, realizado em Itapecerica da Serra, SP, de dezembro de 2012 a maio de 2013. A amostra foi composta por 110 gestantes, com um ou mais partos normais ou cesarianas e 110 primigestas. A força muscular do assoalho pélvico foi avaliada pela perineometria e palpação digital vaginal (Escala de Oxford modificada). RESULTADOS: a média da força muscular do assoalho pélvico em gestantes com antecedentes de parto normal ou cesariana foi 33,4 (desvio-padrão=21,2) cmH2O. Pela escala de Oxford, 75,4% das gestantes com partos ou cesarianas anteriores apresentaram grau ≤2 e 5,5%, grau ≥4; entre as primigestas, 39,9% apresentaram grau ≤2 e 50,9%, grau ≥4, com diferença estatisticamente significante (p<0,001). Pela perineometria, não houve diferença estatisticamente significante entre a força muscular do assoalho pélvico e idade, tipo de parto, paridade, índice de massa corpórea e sintomas do trato geniturinário, mas houve entre as gestantes com e sem antecedente de episiotomia (p=0,04). Na palpação, nenhuma das variáveis mostrou diferença estatisticamente significante. CONCLUSÃO: a gravidez e o parto podem reduzir a força muscular do assoalho pélvico. .

OBJETIVOS: analizar la Fuerza Muscular del Suelo Pélvico (FMSP) de embarazadas con uno o más partos normales o cesáreas; comparar la FMSP de estas embarazadas con la FMSP de primigestas. MÉTODO: estudio transversal con embarazadas hasta 12 semanas de embarazo, realizado en Itapecerica de la Serra, SP, de diciembre de 2012 a mayo de 2013. La muestra fue de 110 embarazadas con uno o más partos normales o cesáreas y 110 primigestas. La FMSP fue evaluada por la perineometría (Peritron(tm)) y palpación digital vaginal (escala de Oxford modificada). RESULTADOS: el promedio de la FMSP en embarazadas con antecedentes de parto normal o cesárea fue 33,4 (de=21,2) cmH2O. Por la escala de Oxford, 75,4% de las embarazadas con partos o cesáreas anteriores presentaron grado ≤ 2 y 5,5%, grado ≥ 4; entre las primigestas, 39,9% presentaron grado ≤ 2 y 50,9%, grado ≥ 4, con diferencia estadísticamente significativa (p<0,001). Por la perineometría, no hubo diferencia estadísticamente significativa entre la FMSP y edad, tipo de parto, número de partos anteriores, índice de masa corporal y síntomas del tracto genitourinario, pero hubo entre las embarazadas con y sin antecedente de episiotomía (p=0,04). En la palpación, ninguna de las variables mostró diferencia estadísticamente significativa. CONCLUSIÓN: el embarazo y el parto pueden reducir la FMSP. .

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The objective of this research work was to design, develop and optimize the self micro-emulsifying drug delivery system (SMEDDS) of Felodipine (FL) filled in hard gelatine capsule coated with polymer in order to achieve rapid drug release after a desired time lag in the management of hypertension. Microemulsion is composed of a FL, Lauroglycol FCC, Transcutol P and Cremophor EL. The optimum surfactant to co-surfactant ratio was found to be 2:1. The resultant microemulsions have a particle size in the range of 65-85 nm and zeta potential value of -13.71 mV. FL release was adequately adjusted by using pH independent polymer i.e. ethyl cellulose along with dibutyl phthalate as plasticizer. Influence of formulation variables like viscosity of polymer, type of plasticizer and percent coating weight gain was investigated to characterize the time lag. The developed formulation of FL SMEDDS capsules coated with ethyl cellulose showed time lag of 5-7 h which is desirable for chronotherapeutic application.

O objetivo desse trabalho de pesquisa foi planejar, desenvolver e otimizar sistema de liberação de fármaco auto-microemulsificante(SMEDDS) de felodipino (FL) em cápsulas de gelatina dura revestidas com polímero, a fim de obter liberação rápida após tempo desejado no manejo da hipertensão. A microemulsão é composta de FL, lauroglilcol FCC, Transcutol P e Cremophor EL. A proporção ótima de tensoativo e de co-tensoativo foi de 2:1. As microemulsões resultantes têm tamanho de partícula na faixa de 65-85 nm com potencial zeta de -13,71 mV. A liberação de FL foi ajustada adequadamente, utilizando-se polímero independente de pH, como etilcelulose com ftalato de dibutila como plastificante. A influência das variáveis da formulação, como viscosidade do polímero, tipo de plastificante e ganho percentual de peso do revestimento foi investigada para caracterizar o intervalo de tempo de liberação. A formulação de cápsulas de FL SMEDDS revestidas com etilcelulose mostrou intervalo de tempo de liberação de 5 a 7 horas, o que é desejável para uma aplicação cronoterapêutica.

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In this study, felodipine was incorporated into microparticles prepared with Eudragit® E and it blended with poly(3-hydroxybutyrate) (PHB) using the emulsion-solvent evaporation technique, with the aim of improving the dissolution rate of the drug. The formulation prepared with Eudragit® E showed irregular and fragmented microparticles, with a loading efficiency (LE) of 82.6%. When the microparticles were prepared with a blend of Eudragit® E and PHB, they had a spherical form with a LE of 103.9%. X-ray diffraction and differential thermal analysis indicated a reduction in the crystallinity of felodipine after its incorporation into the microparticles, which caused a significant increase in the felodipine dissolution rate. An investigation into the absorption in rats was carried out using high-performance liquid chromatography analysis of the blood collected 20 and 60 min after the animals were administered felodipine [30 mg/Kg, orally (p.o.)] or felodipine microparticles (30 mg/Kg, p.o.). Animals that were given felodipine showed mean plasmatic levels of 0.0125 (±0.00156) and 0.0240 (±0.0069) µg mL(-1) after 20 and 60 min, respectively, whereas animals that received microparticles containing felodipine showed respective mean plasmatic levels of 0.0651 (±0.0120) and 0.0369 (±0.0145) µg mL(-1) . Our data suggest that the incorporation into microparticles significantly enhanced the release of felodipine, improving its absorption in rats.

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It has been recently shown that calcium channel blockers might have a protective effect on cardiac fibrogenesis induced by aldosterone. The objective of this study was to evaluate the protective effect of felodipine, a dihydropyridine calcium channel blocker, against heart and kidney damage caused by aldosterone-high sodium intake in uninephrectomized rats. Wistar rats were divided into three groups: CNEP (uninephrectomized + 1% NaCl in the drinking water, N = 9); ALDO (same as CNEP group plus continuous infusion of 0.75 microg/h aldosterone, N = 12); ALDOF (same as ALDO group plus 30 mg*kg(-1)*day(-1) felodipine in the drinking water, N = 10). All results were compared with those of age-matched, untreated rats (CTL group, N = 10). After 6 weeks, tail cuff blood pressure was recorded and the rats were killed for histological analysis. Blood pressure (mmHg) was significantly elevated (P < 0.05) in ALDO (180 +/- 20) and ALDOF (168 +/- 13) compared to CTL (123 +/- 12) and CNEP (134 +/- 13). Heart damage (lesion scores - median and interquartile range) was 7.0 (5.5-8.0) in ALDO and was fully prevented in ALDOF (1.5; 1.0-2.0). Also, left ventricular collagen volume fraction (%) in ALDOF (2.9 +/- 0.5) was similar to CTL (2.9 +/- 0.5) and CNEP (3.4 +/- 0.4) and decreased compared to ALDO (5.1 +/- 1.6). Felodipine partially prevented kidney injury since the damage score for ALDOF (2.0; 2.0-3.0) was significantly decreased compared to ALDO (7.5; 4.0-10.5), although higher than CTL (null score). Felodipine has a protective effect on the myocardium and kidney as evidenced by decreased perivascular inflammation, myocardial necrosis and fibrosis.

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It has been recently shown that calcium channel blockers might have a protective effect on cardiac fibrogenesis induced by aldosterone. The objective of this study was to evaluate the protective effect of felodipine, a dihydropyridine calcium channel blocker, against heart and kidney damage caused by aldosterone-high sodium intake in uninephrectomized rats. Wistar rats were divided into three groups: CNEP (uninephrectomized + 1 percent NaCl in the drinking water, N = 9); ALDO (same as CNEP group plus continuous infusion of 0.75 µg/h aldosterone, N = 12); ALDOF (same as ALDO group plus 30 mg·kg-1·day-1 felodipine in the drinking water, N = 10). All results were compared with those of age-matched, untreated rats (CTL group, N = 10). After 6 weeks, tail cuff blood pressure was recorded and the rats were killed for histological analysis. Blood pressure (mmHg) was significantly elevated (P < 0.05) in ALDO (180 ± 20) and ALDOF (168 ± 13) compared to CTL (123 ± 12) and CNEP (134 ± 13). Heart damage (lesion scores - median and interquartile range) was 7.0 (5.5-8.0) in ALDO and was fully prevented in ALDOF (1.5; 1.0-2.0). Also, left ventricular collagen volume fraction ( percent) in ALDOF (2.9 ± 0.5) was similar to CTL (2.9 ± 0.5) and CNEP (3.4 ± 0.4) and decreased compared to ALDO (5.1 ± 1.6). Felodipine partially prevented kidney injury since the damage score for ALDOF (2.0; 2.0-3.0) was significantly decreased compared to ALDO (7.5; 4.0-10.5), although higher than CTL (null score). Felodipine has a protective effect on the myocardium and kidney as evidenced by decreased perivascular inflammation, myocardial necrosis and fibrosis.

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The absorption and fluorescence properties of nifedipine (NPDHP), felodipine (CPDHP) and a series of structurally related 1,4-dihydropyridines were studied in aqueous solution and organic solvents of different properties. The absorption and fluorescence spectra were found to depend on the chemical nature of the substituents at the position 4 of the 1,4-dihydropyridine ring (DHP) and on solvent properties. In aqueous solution, the fluorescence spectra of 4-phenyl substituted compounds are blue-shifted with respect to the alkyl substituted compounds. The more fluorescent compound is CPDHP. Nifedipine is not fluorescent. All compounds, with the exception of CPDHP, present monoexponential fluorescence decay with very short lifetime (0.2-0.4 ns). CPDHP showed a biexponential emission decay with a long-lived component of 1.7 ns; this behavior is explained in terms of different conformers because of the hindered rotation of the phenyl group by the ortho-substitution. Analysis of the solvent effect on the maximum of the absorption spectrum by using the linear solvent-energy relation solvato-chromic equation indicates the redshifts are influenced by the polarizability, hydrogen bonding ability and the hydrogen bond acceptance of the solvent. Whereas, the fluorescence characteristics (spectra, quantum yields and lifetimes) are sensitive to the polarizabilty and hydrogen bond ability of the solvents. Photo-decomposition of nifedipine is dependent on the solvent properties. Faster decomposition rates were obtained in nonprotic solvents. The 4-carboxylic derivative goes to decarboxylation. Under similar conditions, the other DHP compounds did not show appreciable photodecomposition.

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A rapid, sensitive, robust and specific method was developed for the determination and quantitation of felodipine, in human blood plasma by liquid chromatography coupled with tandem mass spectrometry using nimodipine as internal standard. Felodipine was extracted from 0.5 mL human plasma by use of a liquid/liquid procedure using diethyl ether/hexane (80/20, v/v) as eluent. The method included a chromatographic run of 5 min using a C(18) analytical column (100 mm x 4.6 mm i.d.) and the calibration curve was linear over the range from 0.02 to 10 ng mL(-1) (r(2) > 0.994). The between-run precision, determined as relative standard deviation of replicate quality controls, was 5.7% (0.06 ng mL(-1)), 7.1% (0.6 ng mL(-1)) and 6.8% (7.5 ng mL(-1)). The between-run accuracy was +/- 0.0, 2.1 and 3.1% for the above-mentioned concentrations, respectively.

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PURPOSE: To study the reaction of a series of Hantzsch dihydropyridines with pharmacological significance such as, nifedipine, nitrendipine, nisoldipine, nimodipine, isradipine and felodipine, with electrogenerated superoxide in order to identify products and postulate a mechanism. METHODS: The final pyridine derivatives were separated and identified by gas chromatography/mass spectrometry (GC-MS). The intermediates, anion dihydropyridine and the HO2*/HO2- species, were observed from voltammetric studies and controlled potential electrolysis was used to electrogenerate O2*-. RESULTS: The current work reveals that electrogenerated superoxide can quantitatively oxidize Hantzsch dihydropyridines to produce the corresponding aromatized pyridine derivatives. CONCLUSIONS: Our results indicate that the aromatization of Hantzsch dihydropyridines by superoxide is initiated by proton transfer from the N1-position on the 1,4-dihydropyridine ring to give the corresponding anion dihydropyridine, which readily undergoes further homogeneous oxidations to provide the final aromatized products. The oxidation of the anionic species of the dihydropyridine is more easily oxidized than the parent compound.

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OBJECTIVE: To use published Hypertension Optimal Treatment (HOT) Study data to evaluate changes in cardiovascular mortality in nondiabetic hypertensive patients according to the degree of reduction in their diastolic blood pressure. METHODS: In the HOT Study, 18,700 patients from various centers were allocated at random to groups having different objectives of for diastolic blood pressure:

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