67 research outputs found
p-Dimethylaminobenzaldehyde-reactive substances in tail tendon collagen of streptozotocin-diabetic rats: temporal relation to biomechanical properties and advanced glycation endproduct (AGE)-related fluorescence
AbstractIn the present work, pepsin digests of tail tendons from streptozotocin-diabetic rats were found to contain material that reacted rapidly at room temperature with p-dimethylaminobenzaldehyde (Ehrlich’s reagent) to give an adduct with an absorbance spectrum characteristic of the Ehrlich chromogen of pyrrolic nature determined in ageing collagens. A significant correlation of the Ehrlich adduct with tendon mechanical strength and collagen fluorescence characteristic of advanced glycation endproducts was observed. Collagen content of the Ehrlich-positive material was found to be significantly elevated in tendons of diabetic rats compared with age-matched healthy controls. The results indicate that the p-dimethylaminobenzaldehyde-reactive pyrrole moieties may contribute to the increased cross-linking of diabetic matrix collagen. Profound inhibitory effect of aminoguanidine was observed, underlining the role of non-enzymatic mechanisms of advanced glycation in pyrrolisation and cross-linking of collagen exposed to hyperglycaemia. It is hypothesised that quantification of the p-dimethylaminobenzaldehyde-reactive material in matrix collagen may provide a tissue measure of integrated hyperglycaemia over prolonged periods of time. Further research is to assess the significance of p-dimethylaminobenzaldehyde-reactive substances in diabetic collagen tissues and to reveal their relationship to enzyme-mediated physiological pyrrolisation of ageing collagens
Protective effects of a gastrointestinal agent containing Korean red ginseng on gastric ulcer models in mice
<p>Abstract</p> <p>Background</p> <p>Korean red ginseng (KRG) is a ginseng that has been cultivated and aged for 4-6 years or more, and goes through an extensive cleaning, steaming and drying process. KRG contains more than 30 kinds of saponin components and has been reported as having various biological properties, such as anti-fatigue action, immune restoration, and neurovegetative effect. The purpose of this study was to assess the effects of a KRG-containing drug (KRGCD) on gastric ulcer models in mice.</p> <p>Methods</p> <p>Stomach ulcers were induced by oral ingestion of hydrochloride (HCl)/ethanol or indomethacin. Treatment with KRGCD (30, 100, and 300 mg/kg, p.o.) occurred 1 hr before the ulcer induction. Effect of KRGCD on anti-oxidant activity and gastric mucosal blood flow with a laser Doppler flowmeter in mice stomach tissue was evaluated.</p> <p>Results</p> <p>KRGCD (100 and 300 mg/kg, p.o.) significantly decreased ethanol- and indomethacin-induced gastric ulcer compared with the vehicle-treated (control) group. KRGCD (100 and 300 mg/kg) also decreased the level of thiobarbituric acid reactive substance (TBARS) and increased gastric mucosal blood flow compared with the control group.</p> <p>Conclusions</p> <p>These results suggest that the gastroprotective effects of KRGCD on mice ulcer models can be attributed to its ameliorating effect on oxidative damage and improving effect of gastric mucosal blood flow.</p
Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract
Cataract is one of the earliest secondary complications of diabetes mellitus. The lens is a closed system with limited capability to repair or regenerate itself. Current evidence supports the view that cataractogenesis is a multifactorial process. Mechanisms related to glucose toxicity, namely oxidative stress, processes of non-enzymatic glycation and enhanced polyol pathway significantly contribute to the development of eye lens opacity under conditions of diabetes. There is an urgent need for inexpensive, non-surgical approaches to the treatment of cataract. Recently, considerable attention has been devoted to the search for phytochemical therapeutics. Several pharmacological actions of natural flavonoids may operate in the prevention of cataract since flavonoids are capable of affecting multiple mechanisms or etiological factors responsible for the development of diabetic cataract. In the present paper, natural flavonoids are reviewed as potential agents that could reduce the risk of cataract formation via affecting multiple pathways pertinent to eye lens opacification. In addition, the bioavailability of flavonoids for the lens is considered
Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial
Background
Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS.
Methods
In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358.
Results
Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen.
Conclusions
No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences
Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): A double-blind, randomised controlled trial
Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: analysis of individual data from 94,638 patients treated in 55 breast cancer centers
Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time.
This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails
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Determing Degradation Of Fiberboard In The 9975 Shipping Package By Measuring Axial Gap
Currently, thousands of model 9975 transportation packages are in use by the US Department of Energy (DOE); the design of which has been certified by DOE for shipment of Type B radioactive and fissile materials in accordance with Part 71, Title 10 Code of Federal Regulations (CFR), or 10 CFR 71, Packaging and Transportation of Radioactive Material. These transportation packages are also approved for the storage of DOE-STD-3013 containers at the Savannah River Site (SRS). As such, the 9975 has been continuously exposed to the service environment for a period of time greater than the approved transportation service life. In order to ensure the material integrity as specified in the safety basis, an extensive surveillance program is in place in K-Area Complex (KAC) to monitor the structural and thermal properties of the fiberboard of the 9975 shipping packages. The surveillance approach uses a combination of Non-Destructive Examination (NDE) field surveillance and Destructive Examination (DE) lab testing to validate the 9975 performance assumptions. The fiberboard in the 9975 is credited with thermal insulation, criticality control and resistance to crushing. During surveillance monitoring in KAC, an increased axial gap of the fiberboard was discovered on selected items packaged at Rocky Flats Environmental Technology Site (RFETS). Many of these packages were later found to contain excess moisture. Savannah River National Laboratory (SRNL) testing has resulted in a better understanding of the relationship between the fiberboard moisture level and compaction of the fiberboard under storage conditions and during transport. In laboratory testing, the higher moisture content has been shown to correspond to higher total compaction of fiberboard material and compaction rate. The fiberboard height is reduced by compression of the layers. This change is observed directly in the axial gap between the flange and the air shield. The axial gap measurement is made during the pre-use inspection or during the annual recertification process and is a screening measurement for changes in the fiberboard
The pyridoindole antioxidant stobadine inhibited glycation-induced absorbance and fluorescence changes in albumin
Identification of Novel Aldose Reductase Inhibitors Based on Carboxymethylated Mercaptotriazinoindole Scaffold
Fifteen compounds, sharing an indole-1-acetic
acid moiety as a
common fragment, were selected from commercial databases for testing
aldose reductase inhibition. 3-Mercapto-5<i>H</i>-1,2,4-triazinoÂ[5,6-<i>b</i>]Âindole-5-acetic acid (<b>13</b>) was the most promising
inhibitor, with an IC<sub>50</sub> in the submicromolar range and
high selectivity, relative to aldehyde reductase. The crystal structure
of aldose reductase complexed with <b>13</b> revealed an interaction
pattern explaining its high affinity. Physicochemical parameters underline
the excellent “leadlikeness” of <b>13</b> as a
promising candidate for further structure optimizations
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