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Ghrelin has been implicated in the regulation of gastric functional development, and its physiological functions are mediated by Ghrelin-O-acyltransferase (GOAT) which is capable of generating the active form of this polypeptide hormone. However, whether and how ghrelin gene silencing may modify gastric acid secretion and GOAT-Ghrelin system is yet to be explored. The study was performed in gastric mucosal cells from weanling piglets in vitro. We evaluated the effect of ghrelin on gastric acid secretion, gene expression of GOAT and ghrelin as well as ghrelin levels by RNA interference assay. shGhrelin triggered the down-regulation of ghrelin mRNA expression (P<0.05) via an RNAi mechanism, as observed by real-time RT-PCR. In addition, shGhrelin showed reduced total ghrelin production and secretion (P<0.05) using ELISA in vitro. We also detected that GOAT mRNA expression was reduced in shGhrelin group (P<0.05), compared with control groups. In accordance with the GOAT expression, acylated ghrelin production and secretion were reduced in gastric mucosal cells and culture medium (P<0.05). Silencing of ghrelin gene achieved by RNAi-mediation inhibited the activity of H(+)-K(+)-ATPase and pepsin (P<0.05) in gastric mucosal cells. These results indicated that RNAi of Ghrelin gene inhibited the gastric acid secretion with decreased GOAT mRNA and acylated Ghrelin in gastric mucosal cells.
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Aciltransferases/metabolismo , Mucosa Gástrica/metabolismo , Regulação da Expressão Gênica , Grelina/antagonistas & inibidores , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , RNA Interferente Pequeno/genética , Aciltransferases/genética , Animais , Células Cultivadas , Grelina/genética , Grelina/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/genética , Técnicas In Vitro , Interferência de RNA , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SuínosRESUMO
OBJECTIVE: To assess the status of the cardiovascular disease associated risk levels among hypertensive population of Han, Uygur and Kazakh ethnicities, in Xinjiang Uygur Autonornous Region, to guide hypertension prevention and treatment in different ethnicities. METHODS: Four stages random cluster sampling method was used, and all the data was collected from Xinjiang local residents aged over 18 between October 2007 and March 2010. RESULTS: A total of 14 618 subjects completed this survey, in which 2 654 Han, 1 612 Uygur and 2034 Kazakh people diagnosed with hypertension was included in this research. Most of them were"grade 1 hypertension", and the percentage of grade 3 hypertension was Han (19.1%), Uygur (17.3%) and Kazakh (32.3%), respectively. Majority hypertensive people accompanied with 1 risk factor. The risk proportions of low, medium, high and very high in hypertension population of different ethnicities were Han (19.4%, 34.6%, 46.1%), Uygur (17.7%, 37.6%, 44.7%), Kazakh (12.5%, 38.0%, 49.4%) respectively. In Han, Uygur and Kazakh ethnicities, the percentage of high risk and very high risk was highest in hypertensive men aged over 60 years old.The percentages of hypertension awareness were 42.0%, 45.6%, 46.5% and percentages of medicine therapy were 29.6%, 23.4%, 25.2% for Han, Uygur and Kazakh ethnicities, respectively. CONCLUSIONS: Hypertensive people among Han, Uygur and Kazakh ethnicities in Xinjiang are mainly under high risk and very high risk situation of cardiovascular disease, especially in men aged ≥60. The percentage of hypertension awareness and medicine therapy in high risk and very high risk population is the highest, while percentage of awareness in medium risk population is low.
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Povo Asiático , Doenças Cardiovasculares , Hipertensão , China , Humanos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
We report a measurement of a new high spin Jπ=5- state at 22.4(2) MeV in 12C which fits very well to the predicted (ground state) rotational band of an oblate equilateral triangular spinning top with a D3h symmetry characterized by the sequence 0+, 2+, 3-, 4±, 5- with almost degenerate 4+ and 4- (parity doublet) states. Such a D3h symmetry was observed in triatomic molecules, and it is observed here for the first time in nuclear physics. We discuss a classification of other rotation-vibration bands in 12C such as the (0+) Hoyle band and the (1-) bending mode band and suggest measurements in search of the predicted ("missing") states that may shed new light on clustering in 12C and light nuclei. In particular, the observation (or nonobservation) of the predicted ("missing") states in the Hoyle band will allow us to conclude the geometrical arrangement of the three alpha particles composing the Hoyle state at 7.654 MeV in 12C.
RESUMO
The second J(π)=2+ state of 12C, predicted over 50 years ago as an excitation of the Hoyle state, has been unambiguously identified using the 12C(γ,α0)(8)Be reaction. The alpha particles produced by the photodisintegration of 12C were detected using an optical time projection chamber. Data were collected at beam energies between 9.1 and 10.7 MeV using the intense nearly monoenergetic gamma-ray beams at the HIγS facility. The measured angular distributions determine the cross section and the E1-E2 relative phases as a function of energy leading to an unambiguous identification of the second 2+ state in 12C at 10.03(11) MeV, with a total width of 800(130) keV and a ground state gamma-decay width of 60(10) meV; B(E2:2(2)+â0(1)+)=0.73(13)e(2) fm(4) [or 0.45(8) W.u.]. The Hoyle state and its rotational 2+ state that are more extended than the ground state of 12C presents a challenge and constraints for models attempting to reveal the nature of three alpha-particle states in 12C. Specifically, it challenges the ab initio lattice effective field theory calculations that predict similar rms radii for the ground state and the Hoyle state.
RESUMO
The carbon/oxygen (C/O) ratio at the end of stellar helium burning is the single most important nuclear input to stellar evolution theory. However, it is not known with sufficient accuracy, due to large uncertainties in the cross-section for the fusion of helium with 12C to form 16O, denoted as 12C(α, γ)16O. Here we present results based on a method that is significantly different from the experimental efforts of the past four decades. With data measured inside one detector and with vanishingly small background, angular distributions of the 12C(α, γ)16O reaction were obtained by measuring the inverse 16O(γ, α)12C reaction with gamma-beams and a Time Projection Chamber (TPC) detector. We agree with current world data for the total reaction cross-section and further evidence the strength of our method with accurate angular distributions measured over the 1- resonance at Ecm ~ 2.4 MeV. Our technique promises to yield results that will surpass the quality of the currently available data.
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OBJECTIVE: To evaluate the systemic bioavailability of a new controlled release cyclobenzaprine tablet, and the influence of a high fat meal on its bioavailability. SUBJECTS, MATERIALS AND METHODS: 24 and 12 healthy male subjects were recruited for the bioavailability and influence of diet studies, respectively. Experimental design for both studies was an open randomized, 2-period, single dose, crossover study. In the bioavailability study, each subject received in different occasions, a single oral dose of cyclobenzaprine of immediate (10 mg) or controlled release (20 mg) tablet, followed by a 2-week washout period. In the influence of diet study, the volunteers received the controlled-release tablet concomitantly with a high fat meal or in a state of fasting. RESULTS: In the bioavailability study, plasma cyclobenzaprine profiles were in agreement with a controlled release system. This formulation presented a 92.8% of relative bioavailability (IC 85.5 - 105%) and a significant reduction in Cmax (IC 58 - 65.5%), when compared with equal dose of the immediate release tablet. The presence of food increased AUC (11.6%) and Cmax (48%). For both parameters the calculated 90% confidence interval was not in the bioequivalence interval, 97.4 - 125.8% for AUC and 111.7 - 184.2% for Cmax. CONCLUSIONS: The controlled release tablet showed a relative bioavailability comparable with equal dose of the immediate release product and produced a significantly lower Cmax, as expected in a controlled release formulation. The concomitant administration of the tablet with a high fat meal produced an increase on its bioavailability, mainly in Cmax, with no evidence of dose-dumping.
Assuntos
Amitriptilina/análogos & derivados , Gorduras na Dieta/administração & dosagem , Interações Alimento-Droga , Relaxantes Musculares Centrais/farmacocinética , Adulto , Amitriptilina/administração & dosagem , Amitriptilina/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Preparações de Ação Retardada , Humanos , Masculino , Relaxantes Musculares Centrais/administração & dosagem , Comprimidos , Adulto JovemRESUMO
Fluorescent nanodiamonds (FND) are carbon-based nanomaterials that can efficiently incorporate optically active photoluminescent centers such as the nitrogen-vacancy complex, thus making them promising candidates as optical biolabels and drug-delivery agents. FNDs exhibit bright fluorescence without photobleaching combined with high uptake rate and low cytotoxicity. Focusing on FNDs interference with neuronal function, here we examined their effect on cultured hippocampal neurons, monitoring the whole network development as well as the electrophysiological properties of single neurons. We observed that FNDs drastically decreased the frequency of inhibitory (from 1.81 Hz to 0.86 Hz) and excitatory (from 1.61 to 0.68 Hz) miniature postsynaptic currents, and consistently reduced action potential (AP) firing frequency (by 36%), as measured by microelectrode arrays. On the contrary, bursts synchronization was preserved, as well as the amplitude of spontaneous inhibitory and excitatory events. Current-clamp recordings revealed that the ratio of neurons responding with AP trains of high-frequency (fast-spiking) versus neurons responding with trains of low-frequency (slow-spiking) was unaltered, suggesting that FNDs exerted a comparable action on neuronal subpopulations. At the single cell level, rapid onset of the somatic AP ("kink") was drastically reduced in FND-treated neurons, suggesting a reduced contribution of axonal and dendritic components while preserving neuronal excitability.
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Potenciais de Ação/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Nanodiamantes , Rede Nervosa/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Animais , Células Cultivadas , Hipocampo/fisiologia , Camundongos , Modelos Biológicos , Rede Nervosa/fisiologia , Neurônios/fisiologiaRESUMO
Urinalysis and proteinuria testing represent fundamental tests for the clinician, even though they too often lack standardization. Through the Italian Society of Nephrology Mailing List we sent a questionnaire to 282 centers, in order to assess the state of the art in Italy in the year 2006. 82% of the questionnaires were completed (nephrology laboratories: 64%, general laboratories: 36%). The questionnaire dealt with the main steps of preparation, analysis and report of urinalysis, and proteinuria / microalbuminuria measurement. 85% of the centers use first morning urine, and 7% second morning urine; only 57% of the centers supply with written instructions, 189 laboratories (82%) have only one bright field microscope, rate and time of centrifugation are very varied among centers, different units of measurement are used in reports. Few laboratories measure routinely the proteinuria / creatininuria ratio, there is no agreement on the urine sample type for microalbuminuria assay, total urinary proteins are measured through different methods. 92% of the centers is endowed with an internal quality control system, but only 47% participate in an external quality control program. These data confirm the lack of standardization for urine analysis methods and procedures.
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Urinálise/normas , Humanos , Itália , Inquéritos e QuestionáriosRESUMO
Cytokinesis, the physical separation of daughter cells at the end of cell cycle, is commonly considered a highly stereotyped phenomenon. However, in some specialized cells this process may involve specific molecular events that are still largely unknown. In mammals, loss of Citron-kinase (CIT-K) leads to massive cytokinesis failure and apoptosis only in neuronal progenitors and in male germ cells, resulting in severe microcephaly and testicular hypoplasia, but the reasons for this specificity are unknown. In this report we show that CIT-K modulates the stability of midbody microtubules and that the expression of tubulin ß-III (TUBB3) is crucial for this phenotype. We observed that TUBB3 is expressed in proliferating CNS progenitors, with a pattern correlating with the susceptibility to CIT-K loss. More importantly, depletion of TUBB3 in CIT-K-dependent cells makes them resistant to CIT-K loss, whereas TUBB3 overexpression increases their sensitivity to CIT-K knockdown. The loss of CIT-K leads to a strong decrease in the phosphorylation of S444 on TUBB3, a post-translational modification associated with microtubule stabilization. CIT-K may promote this event by interacting with TUBB3 and by recruiting at the midbody casein kinase-2α (CK2α) that has previously been reported to phosphorylate the S444 residue. Indeed, CK2α is lost from the midbody in CIT-K-depleted cells. Moreover, expression of the nonphosphorylatable TUBB3 mutant S444A induces cytokinesis failure, whereas expression of the phospho-mimetic mutant S444D rescues the cytokinesis failure induced by both CIT-K and CK2α loss. Altogether, our findings reveal that expression of relatively low levels of TUBB3 in mitotic cells can be detrimental for their cytokinesis and underscore the importance of CIT-K in counteracting this event.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Microtúbulos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Tubulina (Proteína)/metabolismo , Animais , Células Cultivadas , Células HeLa , Humanos , Masculino , Camundongos , Microtúbulos/química , Especificidade de Órgãos , FosforilaçãoRESUMO
INTRODUCTION: The exposure to high altitude (H) produces several physiologic alterations which may induce changes in the pharmacokinetics of drugs. This hypothesis has been confirmed in previous studies which suggest that drugs which are highly bound to plasma proteins are most likely to exhibit altered pharmacokinetics. OBJECTIVES: To further elucidate the influence of H on pharmacokinetics, prednisolone was selected, since it is highly bound to plasma proteins, renally excreted and poorly bound to red blood cells. SUBJECTS, MATERIALS AND METHODS: Prednisolone (80 mg) was given orally to three groups of young healthy volunteers. One group was residing at sea level (L): the same volunteers were studied again after 15 hours of exposure to high altitude (3600 m, HA group), and volunteers living at H for at least six months (group HC). RESULTS: There were no statistically significant differences in the pharmacokinetic parameters calculated from plasma data in the three situations studied. When calculated from whole blood data, however, AUC and Cmax were increased and both volume of distribution and clearance diminished after exposure to H, either acute or chronically. Binding to proteins increased significantly after H exposure from 57% in group L to 75% and 94% in group H and HC, respectively. Binding to erythrocytes also increased with H exposure from 43.7% in group L to 50.6% and 61.6% in group HA and HC, respectively. The prednisolone/prednisone ratio in urine was 11.1 in group L, 7.3 in group HA and 45.6 in group HC. CONCLUSION: Since prednisone has very little intrinsic glucocorticoid activity and has to be converted to prednisolone for therapeutic effect, the alteration of the prednisolone/prednisone ratio, as a result of high altitude exposure could be clinically relevant. Additional experiments are desirable to further evaluate this observation.
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Altitude , Anti-Inflamatórios/farmacocinética , Exposição Ambiental , Prednisolona/farmacocinética , Administração Oral , Adulto , Anti-Inflamatórios/administração & dosagem , Humanos , Masculino , Prednisolona/administração & dosagemRESUMO
BK virus-associated nephropathy is an emerging cause of kidney transplant loss. Tapering immunosuppressive drugs and antiviral agents are the only therapy. The diagnosis is based on immunohistochemical findings or polymerase chain reaction on renal biopsy. Phase-contrast microscopy without staining is a simple test to screen the urine of transplant recipients for BK nephritis. Any kidney transplant unit should have the ability to detect decoy cells by phase-contrast microscopy on a spot urine.
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Vírus BK , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/diagnóstico , Urina/virologia , Vírus BK/isolamento & purificação , Creatinina/sangue , Feminino , Humanos , Rim/patologia , Rim/virologia , Transplante de Rim/patologia , Microscopia de Contraste de Fase , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/urina , Complicações Pós-Operatórias/urina , Complicações Pós-Operatórias/virologiaRESUMO
Cat-scratch disease (CSD) is caused by Bartonella henselae and characterized by self-limited fever and granulomatous lymphadenopathy. In some cases signs of a visceral, neurologic, and ocular involvement can also be encountered. In this report we describe the development of CSD in a kidney transplant patient. Immunocompromised hosts are more susceptible to infection from Bartonella compared with the standard population. Infection of Bartonella should be considered as a differential diagnosis in kidney transplant patients with lymphadenopathy of unknown origin.
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Doença da Arranhadura de Gato/diagnóstico , Transplante de Rim/efeitos adversos , Doenças Linfáticas/diagnóstico , Insuficiência Renal/complicações , Animais , Bartonella henselae , Doença da Arranhadura de Gato/microbiologia , Doença da Arranhadura de Gato/terapia , Gatos , Diagnóstico Diferencial , Febre/diagnóstico , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Doenças Linfáticas/complicações , Doenças Linfáticas/etiologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/cirurgiaRESUMO
Limited care dialysis is an interesting option, which has gained attention in several settings because of the aging of the uremic cohort. The aim of this study was to assess its potential in the Piedmont region in northern Italy, evaluating patients' and care-givers' preferences and testing them in a mathematical model of organisation. The study was conducted in the satellite unit of a university hospital (200-210 dialysis patients), following 35 patients (15 at home, 20 in the center, 10 on daily dialysis). Opinions were collected with a questionnaire and features identified were empirically tested through a simulation model. Most patients (34/35) preferred a small unit, with a stable caring team. Further options were flexibility of dialysis schedule, multiple treatment options, integrated center/home care. These needs could be met by a flexible organization including conventional dialysis (3/week) and daily dialysis (6/week). We employed a simulation model (ARENA software) to calculate the nurses required for each shift and the opening hours and best schedule for the unit. Addition of daily dialysis (2-3 hours) to two conventional 4-5 hour sessions to increased the number of patients followed or "spared" beds, ensuring flexibility. According to patients' best choice (7 dialysis stations), and to the recorded calls, the needs are for two nurses per shift, two shifts per day and six nurses for up to 30 patients in limited care. In conclusion, small centers with flexible schedules can tailor dialysis to patients' needs. A managerial approach is valuable for testing cost/benefit ratios in specific contexts.
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Modelos Teóricos , Diálise Renal/métodos , Autocuidado , Adulto , Idoso , Estudos de Viabilidade , Feminino , Administração de Instituições de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do PacienteRESUMO
BACKGROUND: Food-induced changes on the bioavailability of a sustained release lithium carbonate matrix tablet, which uses an acrylic matrix of Eudragit RSPM as sustaining agent, have been studied in healthy male volunteers. The tablet was developed in our laboratory using conventional technology. SUBJECTS, MATERIALS AND METHODS: The study design was a 4 x 4 Latin square involving 12 subjects who received a single dose of the tablet while fasting or with a standardized normal, high fat or high fat/high protein meal. RESULTS: The results showed no differences in half-lifebeta, renal clearance, Vdbeta, AUC, tmax, Xinfinite(u), fraction absorbed and MRT. Higher Cmax (mg/l) were obtained when the tablet was administered with any kind of meal: 2.09 +/- 0.47 (fast), 2.95 +/- 1.04 (normal diet), 2.64 +/- 0.54 (high fat diet) and 2.87 +/- 0.67 (high fat/high protein diet). The analysis of the ratio Cmax/AUC indicated that changes in Cmax were more probably due to changes in the rate of absorption. To evaluate if the magnitude of the change could be clinically relevant, Cmax and C at 12 hours (dosing interval) were treated by the superposition method in order to establish maximum and minimum concentrations at steady-state. For all the experimental conditions both concentrations would remain in the therapeutic range (4.2 10 mg/l or 0.6 - 1.4 mEq/l). CONCLUSION: The behavior of the formulation is appropriate for a sustained release tablet and fasting or non-fasting state seems not to be a major consideration for bioavailability when deciding on the regimen administration.
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Antimaníacos/farmacocinética , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Carbonato de Lítio/farmacocinética , Disponibilidade Biológica , Estudos Cross-Over , Preparações de Ação Retardada , Jejum , Humanos , Carbonato de Lítio/administração & dosagem , Masculino , ComprimidosRESUMO
The result obtained from different studies of the chronopharmacokinetics of some controlled-release tablets of theophylline are variable, since some authors report differences while others do not. At our laboratory we have developed a formulation of a controlled-release theophylline tablet using acrylic resins and we studied the chronopharmacokinetics of theophylline from this dosage form. Seven Caucasian healthy male volunteers participated in the study approved by the Institutional Review Board (IRB). Each volunteer received a controlled release tablet of 300 mg theophylline and an i.v. dose equivalent to 131.46 mg theophylline once at 8.00 a.m. and once at 8.00 p.m. Theophylline plasma concentrations were determined by HPLC. The following pharmacokinetic parameters were calculated: maximum concentration, time to reach maximum concentration, mean residence time, absorption constant, area under the curve of plasma concentration versus time, distribution volume (Vd beta), and total clearance. No statistically significant differences were found between diurnal and nocturnal data. This implied that, with this formulation, there is a lower risk of toxic plasma concentrations or concentrations under the therapeutic level than with formulations that exhibit circadian rhythm.
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Broncodilatadores/farmacocinética , Teofilina/farmacocinética , Adulto , Broncodilatadores/administração & dosagem , Ritmo Circadiano/fisiologia , Preparações de Ação Retardada , Humanos , Injeções Intravenosas , Masculino , Teofilina/administração & dosagemRESUMO
INTRODUCTION: A cascade of pathophysiological events occurs with the ascension to high altitude (H). We have performed studies on the effects of exposure to H on the pharmacokinetics of drugs. The hypothesis behind these studies has been that the exposure to H, which produces marked physiological changes in the body, may alter pharmacokinetics, and consequently, pharmacodynamics. Our previous studies suggest that drugs highly bound to plasma proteins are most likely to exhibit altered disposition. OBJECTIVE: In continuation of our research, we selected furosemide which is about 98% bound to plasma proteins, renally excreted and has low binding to red blood cells. SUBJECTS, MATERIALS AND METHODS: Furosemide (40 mg) was administered orally to 3 groups of young healthy volunteers. One group who had been residing at sea level (group L), the same group after 15 hours of exposure to high altitude (3,600 m, group HA) and a group of volunteers living at H for at least 6 months (group HC). RESULTS: Our results are in accordance with the most recent pharmacokinetic studies on furosemide in which a terminal half-life of approximately 20-30 h was reported. Total proteins were 9.3% and 12.7% higher in groups HA and HC, respectively, than in group L. Albumin in group HC was 8.2% higher than group L. Bilirubin increased 17.7% and 41.2% in groups HA and HC, respectively, in comparison with group L. A rapid disposition rate constant in groups HA and HC was the only pharmacokinetic parameter that was significantly different from those in group L. Concentration of furosemide in plasma water increased significantly after H exposure, thus, the binding diminished from 97.2% in group L to 95.1% and 91.1% in groups HA and HC, respectively. CONCLUSION: Exposure to H produces an increase in the free fraction of furosemide in humans, which could be of therapeutic importance.
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Doença da Altitude/metabolismo , Diuréticos/farmacocinética , Furosemida/farmacocinética , Adulto , Doença da Altitude/sangue , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Diuréticos/sangue , Furosemida/sangue , Meia-Vida , Humanos , MasculinoRESUMO
Food-induced changes on bioavailability of 2 sustained release theophylline matrix tablets, which uses an hydrophilic matrix of Carbopol 974P and lipid matrix of hydrogenated castor oil (Cutina HR) as sustaining agents, have been studied in 2 different groups of 12 healthy male volunteers. The study design was a 4 x 4 Latin square involving 12 subjects who received a single dose of the tablet while fasting or with a standarized normal, high fat or high fat/high protein meal. The results for both formulations showed no differences in t1/2 and MRT when the tablets were administered with any type of diet. No differences in tmax and AUC were found when the Carbopol matrix tablet was administered with any class of diet. Higher Cmax were obtained when the tablet was administered with any class of meal. The analysis of the ratio Cmax/AUC evidenced that changes in Cmax for normal and high fat diet were attributable to higher rate of absorption, probably due to a delay in gastric emptying, thus avoiding the rapid formation of the gel structure which controls the liberation of theophylline. Three subjects showed a probable bioadhesive behavior of the formulation in the fasted condition. The lipid matrix tablet showed a statistical significant delay in tmax comparing the fasted condition with the different diets. AUC, Cmax, and the ratio Cmax/AUC did not change when the tablet was administered with the normal diet. High fat and high fat/high protein diets produced higher AUC (31% and 40%, respectively) and Cmax (40% and 56%, respectively) than under fasting condition. The analysis of the ratio Cmax/AUC indicated that changes in Cmax were more probably due to changes in the amount absorbed. In conclusion, a sustained-release theophylline tablet formulated as a lipid matrix is affected by any meal with a high fat content, probably because of the increase of pancreatic and biliary secretions promoted by the meal that would affect the matrix itself. Normal diet showed this behavior but only as a nonsignificant trend. It seems appropiate to recommend to dose both formulations at least 2 hours before meal, or under consistent conditions of fasting or nonfasting state to assure reproducible absorption or clinical response.
Assuntos
Broncodilatadores/farmacocinética , Interações Alimento-Droga , Teofilina/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Broncodilatadores/administração & dosagem , Broncodilatadores/sangue , Estudos Cross-Over , Preparações de Ação Retardada , Dieta , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Jejum , Esvaziamento Gástrico/fisiologia , Humanos , Absorção Intestinal , Metabolismo dos Lipídeos , Lipídeos/química , Masculino , Comprimidos , Teofilina/administração & dosagem , Teofilina/sangueRESUMO
BACKGROUND: The negative impact of the mass media, the lack of information, and the request for in-depth knowledge are the basis for the present need for educational programs on transplantation, brain death, and chronic kidney diseases end-stage renal disease; (ESRD). The aim of the present article was to critically review the activities performed by Il Gallo di Esculapio, a nonprofit association, in the education on the different phases of ESRD. The associates are physicians and patients, and the activities are integrated institutionally. METHODS: This report is a narrative review of the material produced and performed by Il Gallo di Esculapio ONLUS in 1996-2004. RESULTS: The two main activities developed were book writing and an educational program. Eight books for patient education were written on different aspects of dialysis, transplantation, and ESRD. Most were designed as theses of the Medical School. Cooperation with patients was important in all cases and fundamental for the collection of interviews. EDUCATION: A 4-hour educational program on transplantation started in 2000-2001 (1 high school was involved). The checklist originally included only transplantation and organ donation, but progressively gave space also to dialysis, ESRD, and social health care problems. In 2003-2004 the program involved 67 high schools. The association coordinated progressive patient involvement. CONCLUSION: Small, nonprofit patient-physician associations linked with the University allow enrolling resources for educational activities to often-neglected parts of the medical profession.
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Livros , Educação de Pacientes como Assunto , Relações Médico-Paciente , Humanos , Nefropatias/psicologia , Transplante de Rim/psicologia , Diálise Renal/psicologiaRESUMO
BACKGROUND: Restarting dialysis after kidney transplantation is a critical step with psychological and clinical implications. Maintenance of residual renal function a known factor affecting survival in chronic kidney disease, has so far not been investigated after a kidney transplantation. THE CASE: A 54-year-old woman who started dialysis in 1974 (first graft, 1975-1999) received a second "marginal" kidney graft in February 2001 (donor age, 65 years). Her chronic therapy was tacrolimus and steroids. She had a clinical history as follows: nadir creatinine level of 1.5 mg/dL, moderate-severe hypertension, progressive graft dysfunction, nonresponsiveness to addition of mycophenolate, tapering FK levels, and a rescue switch from tacrolimus to rapamycin. From October to December 2003, the creatinine level increased from 2-2.8 to 7 mg/dL. Biopsy specimen showed malignant and "benign" nephrosclerosis, posttransplantation glomerulopathy, and tacrolimus toxicity. Chronic dialysis was started (GFR <3 mL/min). Rapamycin was discontinued. Dialysis was tailored to reach an equivalent renal clearance of >15 mL/min (2 sessions/wk). Blood pressure control improved, nephrotoxic drugs were avoided, and fluid loss was minimized (maximum 500 mL/hr). By this policy, renal function progressively increased to GFR >10 mL/min in May 2004, allowing a once or twice weekly dialysis schedule, with good clinical balance, and obvious advantages for the quality of life. CONCLUSION: This long-term patient, who restarted dialysis with severely reduced renal function, regained sufficient renal function to allow once weekly dialysis. Thus, careful tailoring of dialysis sessions at the restart of dialysis may allow preservation of residual kidney function, at least in individuals for whom a subsequent graft is unlikely.