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Subsequent Assessments (subsequent + assessment)
Selected AbstractsExamination of the impact of a range of Pluronic surfactants on the in-vitro solubilisation behaviour and oral bioavailability of lipidic formulations of atovaquoneJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2006Leab Sek Exogenous surfactants are increasingly used to enhance the dispersion properties of lipid-based formulations of poorly water-soluble drugs, yet their possible effects on formulation digestion and oral bioavailability in-vivo are not well documented. In this study, in-vitro dispersion and digestion experiments were conducted using formulations comprising a blend of long-chain glycerides, ethanol, a model poorly water-soluble drug (atovaquone), and a series of surfactants including Cremophor EL and a range of Pluronic surfactants (Pluronics L121, L61, L72, L43 and F68). Inclusion of Cremophor EL, a surfactant with a high hydrophilic-lipophilic balance (HLB), promoted complete digestion of the formulation and effective dispersion and solubilisation of the lipolytic products and co-administered drug. Surprisingly, formulations containing the Pluronic (L121) with the lowest HLB (0.5) equally effectively promoted digestion and drug solubilisation and a trend towards decreased digestion and drug solubilisation was observed with Pluronics of increasing HLB values. All formulations effectively prevented drug precipitation, suggesting possible utility in-vivo, and no correlation was evident between the ability of the formulations to self-emulsify on dispersion and to promote drug solubilisation on digestion. Subsequent assessment of the oral bioavailability of atovaquone after administration of formulations containing Cremophor EL or Pluronic L121 or a simple solution of atovaquone in long-chain glycerides confirmed the utility of lipid-based formulations for enhancing the oral bioavailability of poorly water-soluble drugs such as atovaquone, but also indicated that in some cases microemulsion preconcentrate formulations may not provide additional bioavail-ability benefits beyond that achievable using simple lipid solutions. [source] Triggering of dendritic cell apoptosis by xanthohumolMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue S2 2010Nguyen Thi Xuan Abstract Xanthohumol, a flavonoid from beer with anticancer activity is known to trigger apoptosis in a variety of tumor cells. Xanthohumol further has anti-inflammatory activity. However, little is known about the effect of xanthohumol on survival and function of immune cells. The present study thus addressed the effect of xanthohumol on dendritic cells (DCs), key players in the regulation of innate and adaptive immunity. To this end, mouse bone marrow-derived DCs were treated with xanthohumol with subsequent assessment of enzymatic activity of acid sphingomyelinase (Asm), ceramide formation determined with anti-ceramide antibodies in FACS and immunohistochemical analysis, caspase activity utilizing FITC conjugated anti-active caspase 8 or caspase 3 antibodies in FACS and by Western blotting, DNA fragmentation by determining the percentage of cells in the sub-G1 phase and cell membrane scrambling by annexin V binding in FACS analysis. As a result, xanthohumol stimulated Asm, enhanced ceramide formation, activated caspases 8 and 3, triggered DNA fragmentation and led to cell membrane scrambling, all effects virtually absent in DCs from gene targeted mice lacking functional Asm or in wild-type cells treated with sphingomyelinase inhibitor amitriptyline. In conclusion, xanthohumol stimulated Asm leading to caspase activation and apoptosis of bone marrow-derived DCs. [source] Outcome in adulthood of asymptomatic airway hyperresponsiveness in childhood: A longitudinal population studyPEDIATRIC PULMONOLOGY, Issue 3 2002Finn Rasmussen MD Abstract The clinical outcome of asymptomatic airway hyperresponsiveness (AHR) first detected in childhood is sparsely reported, with conflicting results. We used a birth cohort of 1,037 children followed to age 26 years to assess the clinical outcome of asymptomatic AHR to methacholine first documented in study members at age 9 years. Of 547 study members who denied wheezing symptoms ever at age 9 years, 41 (7.5%) showed AHR. Forty showed methacholine responsiveness, with a provocation concentration of methacholine that elicted a 20% drop in forced expired volume in 1 sec (PC20),,,8 mg/mL, and one had baseline airway obstruction with a bronchodilator response exceeding 10%. Of these 41 study members, 18 (44%), 11 (27%), and 4 (10%) maintained AHR in 1, 2, and 3 later assessments, respectively, while 23 (56%) manifested AHR only at age 9. Compared with asymptomatic study members without AHR, those with asymptomatic AHR at age 9 years were more likely to report asthma and wheeze at any subsequent assessment, were more likely to have high IgE levels and eosinophils at ages 11 and 21, and more often demonstrated positive responses to skin allergen testing at ages 13 and 21 years. Persistent AHR at later assessments increased these likelihoods further. In conclusion, asymptomatic children with AHR are more likely to develop asthma and atopy later in life compared with asymptomatic children without AHR. Persistent AHR, even though initially asymptomatic, was associated with an even greater increased risk of development of asthma. We suggest that rather than considering AHR as a marker of asthma, it should be regarded as a parallel pathological process that may lead to subsequent symptoms and clinical evidence of asthma. Pediatr Pulmonol. 2002; 34:164,171. © 2002 Wiley-Liss, Inc. [source] The effect of the levonorgestrel releasing intrauterine system on endometrial hyperplasia: An Australian study and systematic reviewAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2009Melissa J. BUTTINI Background: The levonorgestrel intrauterine system (LNG-IUS) provides effective contraception and treatment for menorrhagia and is used to prevent endometrial hyperplasia (EH) in women taking unopposed oestrogens. Aims: The aim of this study was to assess whether the LNG-IUS was also a safe and effective treatment for EH and to conduct a systematic review of the literature. Methods: A retrospective record review was undertaken in a private gynaecology practice in Brisbane, Australia, and included all women with EH treated with hysterectomy, oral progestins or LNG-IUS between January 2004 and April 2007. Histopathological findings from hysterectomy specimens or endometrial biopsies were used to calculate rates of regression of the EH. Results: Twenty-one women elected to have a hysterectomy and seven of those (33%) had no persisting hyperplasia at surgery. Twenty-six women had a LNG-IUS inserted at initial hysteroscopy dilatation and curettage or shortly afterwards; seven of those elected to proceed to hysterectomy when their diagnosis was known. Among ten women who used oral progestin treatment, 90% showed initial regression; two with recurrent EH were subsequently treated successfully with LNG-IUS. All 21 women (100%), including one with atypia, treated with LNG-IUS for more than seven weeks had normal endometrial histology on subsequent assessment. No women developed endometrial cancer. Pooled analysis of the published literature gave a 96% regression rate for non-atypical EH treated with LNG-IUS. Conclusions: These data contribute further evidence that LNG-IUS is a safe and effective method for treating non-atypical EH. Whether LNG-IUS could provide a safe and cost-effective alternative to hysterectomy for atypical EH warrants further examination. [source] Effects of dilution on the exposure in sediment toxicity tests,buffering of freely dissolved concentrations and changes in mixture compositionENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2007Thomas L. ter Laak Abstract Some sediment toxicity tests, such as the Microtox® test, are conducted by diluting either contaminated sediment or an aqueous phase with clean water. The present study aims to clarify how the dilution procedure affects the exposure of organisms. It is shown that freely dissolved concentrations of hydrophobic compounds are buffered by desorption from the sediment matrix when sediment is diluted with water. The buffering depends on the properties of the sediment matrix and contaminant. Consequently, the composition of a contaminant mixture changes with dilution, and the exposure in a sediment dilution toxicity test is poorly defined. This questions the application and subsequent assessments of such tests. Additionally, the often-observed higher toxicity in sediment dilution tests relative to elutriate dilution tests is not sufficient to claim direct contact exposure, because the enhanced sensitivity in sediment dilution tests also can be explained by buffering from the sediment matrix. In applying these tests, one should be aware of the fundamental differences between the sediment dilution strategy and the dilution of an aqueous phase and of the consequences it has for the outcome of the test. [source] MEGX disposition in critically-ill trauma patients: subsequent assessments during the first week following traumaFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2002Federico Pea ABSTRACT The objective of this study was to evaluate MEGX disposition as a surrogate marker in assessing the influence that injury may exert on liver function during the first week after the traumatic event in young vs. elderly patients. The MEGX exposure over time was assessed at 0.25, 0.5, 1, 2, 4 and 6 h after the intravenous administration of a 1 mg/kg lidocaine test dose in 12 young and 7 elderly trauma patients on days1, 4 and 7 after a severe injury (Apache II score > 10). MEGX plasma concentration,time profiles were consistently different on day 1 in the elderly vs. young, consistent with a statistically significant lower rate of both lidocaine clearance and MEGX formation, and with a considerably longer MEGX elimination in the elderly than in the young. This suggests an impairment of liver blood flow as a result of splanchnic vasoconstriction occurring mainly in elderly trauma patients. A significant improvement in MEGX disposition occurred on days 4 and 7 vs. the day of trauma in most elderly, whereas minor changes were observed in the young. Multiple factors may account for these major changes in the elderly: the more severe status, the major sensitivity to the pathophysiologic changes induced by trauma, and also at least partially the ageing processes. Although referring to a limited number of observations, our findings on MEGX disposition suggest that liver function may be affected by the severity of injury, even if the influence of age should not be underestimated in these patients. [source] Outcome of active disease in ankylosing spondylitis: A prospective studyMUSCULOSKELETAL CARE, Issue 1 2010Grad Dip Phys, J. Martindale PhD Abstract Background:,People with ankylosing spondylitis (AS) typically experience episodic exacerbations, but the extent to which they subsequently experience a sustained reduction in disease markers below recognized thresholds for active disease is unclear. Objective:,To investigate changes in, and associations between, disease markers over 18 months in people with active AS. Methods:,Within a cohort of 89 participants with AS, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of 4 or higher were used to identify those with active disease. Standard assessment tools were used to monitor participants prospectively at four consecutive six-monthly intervals. Participants received standard treatments but none received anti-tumor necrosis factor-alpha (TNF,) medication during the study. Results:,The median age of the cohort was 50 years (inter-quartile range [IQR] 38.5,55.5), the median age of disease onset was 25 years (IQR 18,33) and the median disease duration was 18 years (IQR 13,27). Forty-seven (53%) participants had a BASDAI score of 4 or higher on the first assessment, of whom 45 (51%) scored 4 or higher on all subsequent assessments. Furthermore, 38 (43%) and 16 (18%) participants scored BASDAI 5 or 6, respectively, or higher, throughout. BASDAI scores correlated strongly with Bath Ankylosing Spondylitis Functional Index (BASFI) scores. Compared with 19 (21%) participants whose BASDAI scores were consistently below 4 throughout, participants with persistently high BASDAI scores showed higher scores for anxiety and depression, and some evidence of functional deterioration during the study period. Conclusions:,In this cohort, disease markers in most people with active AS were sustained above the standard threshold for active disease. This has important implications for planning care pathways and for optimal utilization of anti-TNF, treatment. Copyright © 2009 John Wiley & Sons, Ltd. [source] Quantifying successional changes in response to forest disturbancesAPPLIED VEGETATION SCIENCE, Issue 2 2008Trent D. Penman Question: Can dissimilarity measures of individual plots be used to forecast the driving factors among various anthropogenic disturbances influencing understorey successional changes? Location: Yambulla State Forest, south-eastern Australia (37°14'S, 149°38'E). Methods: Assessments of understorey vegetation communities were taken prior to anthropogenic disturbances and at three subsequent time periods representing a period of 15 years post-disturbance. Dissimilarities were calculated from the original assessment and modelled in a Bayesian framework to examine the influence of logging, number of prescribed burns and time. Results: All sites underwent significant changes over time independently of the imposed management regimes. Logging resulted in an immediate change in vegetation assemblage which decreased in the subsequent assessments. The number of prescribed fires brought greater change in the shrub vegetation assemblages, but less change in the ground species vegetation assemblages. Conclusions: The anthropogenic disturbances did have some role in the changes of vegetation assemblages but these were minimal. The ongoing changes appear to be a natural response to the last wildfire, which passed through the study area in 1973 (13 years prior to the study). Forest management practices should consider the influence of wildfire succession when planning for the conservation of biodiversity. [source] | |||||||||||||