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991.
Bill J Gurley Ashley Swain Gary W Barone D Keith Williams Philip Breen C Ryan Yates Leslie B Stuart Martha A Hubbard Yudong Tong Sreekhar Cheboyina 《Drug metabolism and disposition》2007,35(2):240-245
Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo. 相似文献
992.
B Sarmento D C Ferreira L Jorgensen M van de Weert 《European journal of pharmaceutics and biopharmaceutics》2007,65(1):10-17
The aim of the present study was to probe the structural integrity of insulin after being entrapped into chitosan/alginate nanoparticles produced by ionotropic polyelectrolyte pre-gelation. By manipulating the alginate:chitosan mass ratio and the pH during nanoparticle production, desired nanoparticles with a mean size of 850 (+/-88)nm and insulin association efficiency of 81 (+/-2)% were obtained. Insulin secondary structure was assessed by Fourier transform infrared (FTIR) and circular dichroism (CD) after entrapment into nanoparticles and after release from the particles under gastrointestinal simulated conditions. FTIR second-derivative spectra and area-overlap compared to an insulin standard confirmed that no significant conformational changes of insulin occurred in terms of alpha-helix and beta-sheet content. Far-UV-CD spectra corroborated the preservation of insulin structure during the nanoparticle production procedure. The presented nanoparticulate system is a promising carrier for insulin oral delivery since it preserves insulin structure and therefore also, potentially, its bioactivity. 相似文献
993.
994.
AIMS: In normotensive women with Type 1 diabetes and microalbuminuria we previously found preterm delivery (< 34 weeks) in 23% of the pregnancies. Antihypertensive treatment was initiated in late pregnancy when preeclampsia was diagnosed and diastolic blood pressure > 90 mmHg. From April 2000 our routine was changed and early antihypertensive treatment with methyldopa was initiated if antihypertensive treatment was given prior to pregnancy, if urinary albumin excretion (UAE) was > 2 g/24 h, or blood pressure > 140/90 mmHg. The present study describes the impact of this more aggressive antiypertensive treatment in the prevalence of preterm delivery. METHODS: The old cohort (1995-1999) consisted of 26 and the new cohort (2000-2003) of 20 pregnant women with Type 1 diabetes and microalbuminuria. All were referred before gestational week 17. RESULTS: The cohorts were comparable with regard to age, diabetes duration, prepregnancy body mass index, HbA1c, blood pressure 121 (13)/71 (8) vs. 121 (14)/73 (8) mmHg [mean (sd)] and early UAE 69 (16-278) vs. 74 (30-287) mg/24 h (geometric mean and range). Antihypertensive treatment was initiated in the old cohort at 29 (20-33) weeks, n = 9, and in the new at 13 (0-34) weeks, n = 10. The prevalence of preterm delivery before 34 weeks was reduced from 23% to zero (P = 0.02), preterm delivery before 37 weeks from 62% to 40% (P = 0.15) and preeclampsia from 42% to 20% (P = 0.11). Perinatal mortality occurred in 4% vs. 0%. Birth weight was 3124 (767) g vs. 3279 (663) g. CONCLUSION: Introduction of early antihypertensive treatment with methyldopa in normotensive pregnant women with Type 1 diabetes and microalbuminuria resulted in a significant reduction in preterm delivery before gestational week 34. 相似文献
995.
Inflammation Research - . 相似文献
996.
997.
Chang Y Jung Hyo S Choi Jin S Ju Hyo S Park Tae G Kwon Yong C Bae Dong K Ahn 《The journal of pain》2006,7(10):747-756
The present study investigated the role of central metabotropic glutamate receptors (mGluRs) in interleukin-1beta (IL-1beta)-induced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Experiments were carried out on male Sprague-Dawley rats weighing 230 to 280 g. After administration of 0.01, 0.1, 1, or 10 pg of IL-1beta into a subcutaneous area of the vibrissa pad, we examined the withdrawal behavioral responses produced by 10 successive trials of an air-puff ramp pressure applied ipsilaterally or contralaterally to the IL-1beta injection site. Subcutaneous injection of IL-1beta produced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Intracisternal administration of CPCCOEt, a mGluR1 antagonist, or MPEP, a mGluR5 antagonist, reduced IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia. Intracisternal administration of APDC, a group II mGluR agonist, or L-AP4, a group III mGluR agonist, reduced both IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia. The antiallodynic effect, induced by APDC or L-AP4, was blocked by intracisternal pretreatment with LY341495, a group II mGluR antagonist, or CPPG, a group III mGluR antagonist. These results suggest that groups I, II, and III mGluRs differentially modulated IL-1beta-induced mechanical allodynia, as well as mirror-image mechanical allodynia, in the orofacial area. PERSPECTIVE: Central group I mGluR antagonists and groups II and III mGluR agonists modulate IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Therefore, the central application of group I mGluR antagonists or groups II and III mGluR agonists might be of therapeutic value in treating pain disorder. 相似文献
998.
L. van den Bemt M. P. de Vries L. van Knapen M. Jansen M. Goossens J. W. M. Muris C. P. van Schayck 《Clinical and experimental allergy》2006,36(2):233-237
BACKGROUND: Exposure to a high level of house dust mite allergens (HDMAs) is considered as a risk factor for HDM sensitization and development of asthma in genetically disposed people. Mattresses are one of the most important sources of HDMA in people's living environment. OBJECTIVE: The aim of this study was to evaluate the association between mattress characteristics and HDMA concentrations on mattresses. METHODS: Dust samples of mattress surfaces were taken to evaluate the level of Der p 1 allergen. All participants filled in a questionnaire about the type of mattress, the type of covering (upper layer) of the mattress, dwelling characteristics and cleaning habits. Humidity and temperature of the bedroom were measured at the time of dust sampling. RESULTS: One hundred and sixty-eight questionnaires were filled in. Synthetic upper layer of the mattress was associated with a higher level of Der p 1 compared with cotton upper layer (2.6 vs. 0.8 microg/g Der p 1). Moreover, higher relative humidity (RH) was associated with significant higher concentrations and density of Der p 1. CONCLUSIONS: Two factors were associated with lower levels of Der p 1 found on mattresses, namely: a cotton upper layer of the mattress compared with a layer of synthetic material and lower RH at the time of sampling. As far as we know, the association between type of upper layer and concentration of Der p 1 has not been described before and could lead to the formulation of practical advices in order to reduce HDMA concentrations on mattresses. 相似文献
999.
Pyroglutamyl, proline-rich oligopeptides, classically referred to as bradykinin-potentiating peptides (BPPs) are found in Bothrops jararaca venom, and are naturally occurring inhibitors of the somatic angiotensin-converting enzyme (ACE). The chemical and pharmacological properties of these peptides were essential for the development of captopril, the first active site directed inhibitor of ACE, currently used to treat human hypertension. ACE is a complex ectoenzyme of the vascular endothelium, possessing two catalytic sites, performing diverse specific roles. Recent advances concerning novel features of BPPs revealed that they might still contribute to a better understanding of the cardiovascular physiology and pathology. The molecular biology of the BPPs revealed that they are part of two distinct C-type natriuretic peptide precursors found in the venom gland and the brain of B. jararaca, each containing seven BPPs. In situ hybridization studies detected the presence of the corresponding mRNA precursor in snake brain regions correlated with neuroendocrine functions, such as the ventro-medial hypothalamus, the paraventricular nuclei, the paraventricular organ, and the subcommissural organ. In this article we discuss the large variety of homologous BPPs in B. jararaca venom and brain, its significance, and whether the BPPs could represent novel endogenous neuropeptides. 相似文献
1000.