Experiments were designed to determine the effects of glutathione (GSH) depletion with L-buthionine sulfoximine (BSO) or diethyl maleate (DEM) on tissue and plasma prostacyclin (6-keto-PGF1 alpha) and thromboxane (TxB2) levels in male Sprague-Dawley rats. Despite depleting hepatic GSH to as much as 34% of control, BSO at various levels (0.4, 0.8 and 1.2 g/kg body wt) had no effect on hepatic, renal, pulmonary or cardiac tissue levels of 6-keto-PGF1 alpha and TxB2 or circulating levels of 6-keto-PGF1 alpha in portal or arterial plasma. When rats were pretreated with 3-methylcholanthrene (3-MC) to induce cytochrome P450, BSO (0.8 g/kg body wt) also had no effect on tissue or plasma prostanoid levels with the exception of a slight, but significant, increase in hepatic 6-keto-PGF1 alpha in non-induced rats. In contrast, depletions of hepatic, renal and pulmonary tissue GSH by DEM (1 mL/kg body wt) to 12, 50 and 30% of control, respectively, were associated with elevations of 6-keto-PGF1 alpha in these tissues and in plasma obtained by right ventricular heart puncture. Pretreatment of rats with 3-MC had no significant effect on tissue GSH or prostanoid levels in controls or DEM-treated rats but plasma levels of 6-keto-PGF1 alpha were lower in comparison to non-induced rats. DEM with or without 3-MC pretreatment was associated with increased TxB2 in renal tissue, whereas DEM elevated TxB2 only in pulmonary tissue from non-induced rats. It appears that factors besides GSH depletion may be required to raise plasma and/or tissue 6-keto-PGF1 alpha levels in vivo. 相似文献
The gastrointestinal (GI) side-effects of dietary fibers are recognized, but less is known about their effects on non-GI symptoms. We assessed non-GI symptoms in a trial of the LDL-cholesterol lowering effect of oat β-glucan (OBG). Participants (n = 207) with borderline high LDL-cholesterol were randomized to an OBG (1 g OBG, n = 104, n = 96 analyzed) or Control (n = 103, n = 95 analyzed) beverage 3-times daily for 4 weeks. At screening, baseline, 2 weeks and 4 weeks participants rated the severity of 16 non-GI symptoms as none, mild, moderate or severe. The occurrence and severity (more or less severe than pre-treatment) were compared using chi-squared and Fisher’s exact test, respectively. During OBG treatment, the occurrence of exhaustion and fatigue decreased versus baseline (p < 0.05). The severity of headache (2 weeks, p = 0.032), anxiety (2 weeks p = 0.059) and feeling cold (4 weeks, p = 0.040) were less on OBG than Control. The severity of fatigue and hot flashes at 4 weeks, limb/joint pain at 2 weeks and difficulty concentrating at both times decreased on OBG versus baseline. High serum c-reactive-protein and changes in c-reactive-protein, oxidized-LDL, and GI-symptom severity were associated with the occurrence and severity of several non-GI symptoms. These data provide preliminary, hypothesis-generating evidence that OBG may reduce several non-GI symptoms in healthy adults. 相似文献
To determine predictive/prognostic factors for patients with metastatic breast cancer (MBC) receiving first-line monochemotherapy using biomarker analysis and geriatric assessment (GA).
Materials and Methods
Karnofsky Performance Status (KPS) and GA as clinical parameters, and prognostic inflammatory and nutritional index (PINI), and Glasgow prognostic score (GPS) as biomarkers were analyzed for association with clinical outcome within the randomized phase III PEg-LIposomal Doxorubicin vs. CApecitabin iN MBC (PELICAN) trial of first-line pegylated liposomal doxorubicin (PLD) or capecitabine.
Results
Of 210 patients, 38% were > 65 years old. GA (n = 152) classified 74% as fit, 10% as compromised, and 16% as frail. Biomarkers showed no age dependency. In multivariate analysis (n = 70) KPS, GA, cumulative illness rating scale-geriatrics (CIRS-G), and GPS were significantly associated with time to progression, and KPS, CIRS-G, and instrumental activities of daily living (IADL) from GA, and PINI showed a significant correlation with overall survival.
Conclusion
GA evaluation was feasible. KPS significantly correlated with efficacy outcomes. Items of a GA and biomarkers of inflammation and nutrition may have prognostic significance in patients with MBC. 相似文献
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Im Rahmen des Projekts „IMOA – Improving Health Monitoring in Older Age“ sollen Grundlagen für ein... 相似文献
Context: In this study, controlled ciprofloxacin (CIPRO) nanostrustructured lipid carriers of Precirol® ATO 5/Transcutol® HP (batch A) and tallow fat/Transcutol® HP (batch B) was carreid out. Objective: The aim was to improve solubility and bioavailability of CIPRO.
Objective: Study of controlled ciprofloxacin (CIPRO) nanostructured lipid carriers of Precirol® ATO 5/Transcutol® HP (batch A) and tallow fat/Transcutol® HP (batch B).
Methods: CIPRO concentrations C1–5 (0.0, 0.2, 0.5, 0.8, and 1.0% w/w) as AC1–5 and BC1–5 were prepared by hot homogenisation and characterised by zetasizer, differential scanning calorimetry, Fourier transform infra-red spectroscopy, in vitro drug release and growth inhibitory zone diameter (IZD) on agar-seeded Bacillus subtilis.
Results: AC5 achieved polydispersed particles of ~605?nm, 92% encapsulation efficiency (EE) and –28?mV similar to BC5 (~789?nm, 91% EE, and –31?mV). Crystallinity indices (AC5 and BC5) were low at 3 and 5%, respectively. CIPRO release in AC5 was ~98% in SGF (pH 1.2) and BC5 similarly ~98% in SIF (pH 6.8).
Conclusions: AC5 had superior growth inhibition of B. subtilis at lower concentration (1.2 µg/mL) than BC5 and CIPRO controls; hence could serve as possible sustained delivery system of CIPRO. 相似文献
In this systematic literature review, we identify evidence on the effectiveness of nudges in improving the self-management of adults with chronic diseases and derive policy recommendations. We included empirical studies of any design published up to April 12th, 2018. We synthesized the results of the studies narratively by comparing statistical significance and direction of different nudge types’ effects on primary study outcomes. Lastly, we categorized the nudges according to their degree of manipulation and transparency.We identified 26 studies, where 13 were of high or moderate quality. The most commonly tested nudges were reminders, planning prompts, small financial incentives, and feedback. Overall, 8 of 9 studies with a high or moderate quality ranking, focused on self-management outcomes, i.e., physical activity, attendance, self-monitoring, and medication adherence, found that nudges had significant positive effects. However, only 1 of 4 studies of high or moderate quality, analyzing disease control outcomes (e.g., glycemic control), found that nudges had a significant positive effect for one intervention arm.In summary, this review demonstrates that nudges can improve chronic disease self-management, but there is hardly any evidence to date that these interventions lead to improved disease control. Reminders, feedback, and planning prompts appear to improve chronic disease self-management most consistently and are among the least controversial types of nudges. Accordingly, they can generally be recommended to policymakers. 相似文献