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91.
Dinkova-Kostova AT Cheah J Samouilov A Zweier JL Bozak RE Hicks RJ Talalay P 《Medicinal chemistry (Shāriqah (United Arab Emirates))》2007,3(3):261-268
The implications of oxidative stress in the pathogenesis of many chronic human diseases has led to the widely accepted view that low molecular weight antioxidants could be beneficial and postpone or even prevent these diseases. Small molecules of either plant or synthetic origins, which contain Michael acceptor functionalities (olefins or acetylenes conjugated to electron-withdrawing groups) protect against the toxicity of oxidants and electrophiles indirectly, i.e., by inducing phase 2 cytoprotective enzymes. Some of these molecules, e.g., flavonoid and curcuminoid analogues that have phenolic hydroxyl groups in addition to Michael acceptor centers, are also potent direct antioxidants, and may therefore be appropriately designated: bifunctional antioxidants. By use of spectroscopic methods we identified phenolic chalcone and bis(benzylidene)acetone analogues containing one or two Michael acceptor groups, respectively, as very efficient scavengers of two different types of radicals: (a) the nitrogen-centered 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS.+) radical cation, and (b) the oxygen-centered galvinoxyl (phenoxyl) radical. The most potent scavengers are those also bearing hydroxyl substituents on the aromatic ring(s) at the ortho-position(s). The initial reaction velocities are very rapid and concentration-dependent. In the human keratinocyte cell line HaCaT, the same compounds coordinately increase the intracellular levels of glutathione, glutathione reductase, and thioredoxin reductase. Thus, such bifunctional antioxidants could exert synergistic protective effects against oxidants and electrophiles which represent the principal biological hazards by: (i) scavenging hazardous oxidants directly and immediately; and (ii) inducing the phase 2 response to prevent and resolve the consequences of hazardous processes that are already in progress, i.e., acting indirectly, but with much more diverse and long-lasting effects. 相似文献
92.
Single‐tube tetradecaplex panel of highly polymorphic microsatellite markers < 1 Mb from F8 for simplified preimplantation genetic diagnosis of hemophilia A 下载免费PDF全文
93.
94.
Ronday HK; Te Koppele JM; Greenwald RA; Moak SA; De Roos JA; Dijkmans BA; Breedveld FC; Verheijen JH 《Rheumatology (Oxford, England)》1998,37(1):34-38
The plasminogen activation system is one of the enzyme systems held
responsible for bone and cartilage degradation in rheumatoid arthritis
(RA). In this study, we evaluated the effect of tranexamic acid (TEA), an
inhibitor of plasminogen activation, on urinary collagen cross-link
excretion and radiological joint damage in rat adjuvant arthritis (AA) and
on urinary collagen cross-link excretion in patients with RA. In the animal
study, adjuvant arthritis was induced in male Lewis rats. From day 7
onward, high-dose TEA (500 mg/kg body weight, once daily) or placebo was
administered orally. Study groups consisted of TEA-treated normal rats (C +
TEA), placebo-treated normal rats (C + plac), AA rats treated with TEA (AA
+ TEA) or with placebo (AA + plac). To monitor joint destruction, urinary
collagen cross-link excretion (pyridinoline, HP; deoxypyridinoline, LP) was
measured by high-performance liquid chromatography at days 14 and 21.
Radiological evaluation of joints was performed at day 21. In the patient
study, TEA was administered to nine patients with RA as adjuvant medication
(approximately 20 mg/kg body weight, three times daily) for 12 weeks.
Urinary HP and LP excretion levels were measured before and during TEA
treatment, and 4 weeks after the cessation of TEA treatment. In AA + TEA
rats, a significant reduction of HP and a tendency towards a reduction of
LP excretion were found compared with AA + plac rats (P < 0.05), at day
14, whereas the HP/LP ratio did not change. No difference was observed in
HP, LP excretion, HP/LP ratio and radiological damage score between the
TEA- and placebo-treated AA rats at day 21. In RA patients, a significant
reduction of HP and LP excretion was found during the TEA treatment period
(P < 0.05). After the cessation of TEA treatment, HP and LP excretion
increased towards baseline levels. No effect on disease activity was
observed. The plasmin antagonist TEA reduced the excretion of collagen
pyridinoline cross-links in both experimental and rheumatoid arthritis. As
such, this study not only supports the involvement of the plasminogen
activation system in the destructive phase of arthritis, but also suggests
a beneficial effect of therapeutic strategies directed against inhibition
of matrix proteolysis.
相似文献
95.
A. C. Thai W. Y. Ng K. Y. Loke W. R. W. Lee K. F. Lui J. S. Cheah 《Diabetologia》1997,40(12):1425-1430
Summary An autoimmune basis for the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is supported by the frequent presence
of autoantibodies – islet cell antibodies (ICAs) and GAD antibodies (GADab). However, in Chinese patients with clinical IDDM,
a low prevalence of ICAs was observed. In non-insulin-dependent diabetic (NIDDM) patients, it has been suggested that the
presence of GADab may identify a subset of latent autoimmune diabetes in adults (LADA). We determined the frequency of GADab
in a large group of 134 IDDM and 168 NIDDM Chinese patients, and assessed the relation with ICAs status. Results showed that
39.6 % IDDM and 16.1 % NIDDM patients had GADab, and 20.1 % and 4.8 %, respectively had detectable ICAs. Frequency of GADab
positivity was not influenced by whether the patients had youth or adult-onset IDDM or NIDDM, or by duration of diabetes.
NIDDM patients seropositive for GADab shared similar clinical characteristics and fasting C-peptide levels with those who
were GADab negative. Presence of GADab therefore did not serve to identify a sub-group of patients with latent or slow-onset
IDDM. Half (53 %) of our IDDM patients had neither GADab nor ICAs. The reason for this observation is unclear. One theory
is that other autoantigens yet to be identified may be contributory. Alternatively, in the Chinese, autoimmunity may not be
the major factor in the pathogenesis of IDDM. [Diabetologia (1997) 40: 1425–1430]
Received: 11 March 1997 and in revised form: 13 May 1997 相似文献
96.
Heterotypic adherence between marrow stromal cells (MSC) and lymphoblastic cells is essential for normal lymphopoiesis and malignant lymphoblastic development. However, the detailed molecular mechanisms by which this heterotypic adherence occurs are poorly understood. The cell-cell interactions between a B-lymphoblastic cell line (UTMB-460) and a pre-B-cell line (NALM-6) with MSC were chosen as models to investigate potential mechanisms and adhesion molecules involved in the apposition between normal and malignant lymphoblastic cells and MSC. A parallel-flow detachment assay (PFDA) and a 51Cr detachment assay, coupled with monoclonal antibody (MoAb) blocking experiments, were used to quantify the attachment of lymphoblastic cells to confluent monolayers of MSC. The apposition between MSC and B-lymphoblastic cells (UTMB-460 cells) was investigated for variable time periods, ranging from 1 minute to 4 hours. Results from the temporal study suggest that the heterotypic adherence of the B-lymphoblastic cells to MSC is a biphasic event and the interactions occur rapidly (< or = 1 minute) after the two cells come into contact. More specifically, the early phase of adherence (< or = 15 minutes) solely involves very late antigen-4 alpha (VLA-4 alpha)/vascular cell adhesion molecule 1 (VCAM- 1) interactions, as evidenced by the nearly complete inhibition (93%) of UTMB-460 cell adherence in the presence of anti-VLA-4 alpha. The late phase (> or = 30 minutes) proceeds despite the continuous presence of anti-VLA-4 alpha. In addition, the late-phase adherence is not affected by MoAbs to LFA-1, CD44, VCAM-1, E-selectin, or L-selectin, which suggests the possible involvement of other adhesion molecules. Adherence of pre-B-lymphoblastic cells (NALM-6) to MSC is also biphasic. Integrin VLA-4 is again a major player in the early phase of pre-B-lymphoblastic cell/MSC interactions. The early phase of adherence may be important in homing of the malignant lymphoblastic cells to the MSC and the late phase in retention of malignant lymphoblastic cells in the bone marrow. 相似文献
97.
OBJECTIVE: To determine the medical conditions for which oral corticosteroids are prescribed and to determine the frequency and type of osteoporosis prophylaxis offered to these patients. METHODS: Medical records of all inpatients for the period March to October 1999 who were documented in pharmacy records as either having received continuous oral steroids for at least 3 months or who had at least 4 courses of oral steroids per year were examined for the following data: age, sex, medical condition for which steroids were required, dose and duration of steroid therapy, whether they were offered bone mineral density (BMD) scans, and whether they were offered drug prophylaxis for steroid induced osteoporosis and the type of drug prophylaxis offered. Followup telephone calls were made to verify patients' use of prophylactic treatment and to validate the chronic use of oral corticosteroids. Use of BMD testing was also validated by comparing the list of patients in this study with the records of bone densitometer units in the area. RESULTS: A total of 189 medical records were examined: 38% were women (n = 72) and 62% were men (n = 117), with an age range of 19-91 years; 73% were taking continuous steroid therapy, the remaining 27% had multiple courses of prednisolone through the year. Steroids were prescribed for respiratory (n = 82, 43%), rheumatological (n = 74, 39%), hematological (n = 16, 8%), dermatological (n = 8, 4%), and gastrointestinal conditions (n = 7, 4%). Chronic obstructive airway disease was the most common respiratory condition for which steroids were prescribed (77, 94%), and polymyalgia rheumatica (36%) and inflammatory arthritis (41%) were the most common rheumatological conditions for which steroids were prescribed. In total, 47% (n = 89) were offered BMD scans while 53% (n = 100) were not. Of the 100 patients not offered BMD scans, 21 (21%) were receiving some form of drug prophylaxis, while 79% of patients were not taking any form of drug prophylaxis. Prophylaxis consisted of calcitriol (64%), alendronate (11%), calcitriol and calcium (7%), calcium alone (7%), alendronate and calcium (3%), etidronate and calcium (2%), alendronate, calcitriol and calcium (1%), alendronate and calcitriol (1%), and hormone replacement therapy (4%). Rheumatologists utilized both BMD testing and prophylactic treatment twice as often in patients taking chronic oral corticosteroid treatment than other specialty physicians. CONCLUSION: Compared to literature reports, the use of prophylaxis for corticosteroid induced osteoporosis was relatively high at this teaching hospital, with a surprisingly large number of patients receiving this treatment with no monitoring by BMD measurements. 相似文献
98.
99.
Simultaneous sonography and quantitative serum human chorionic gonadotropin (HCG) levels from 126 women with threatened abortion were compared. Of 56 women with normal outcome, 39 (70%) had a gestation sac greater than or equal to 5 mm in mean sac diameter, and in each case the HCG level was 1,800 milli-international units (mIU/ml) or greater. The serum HCG levels strongly correlated with the gestation sac sizes to a mean sac diameter of 25 mm. Of 70 abnormal pregnancies, 31 demonstrated a gestation sac. Of these, 20 women (65%) had disproportionately low HCG levels relative to sac size, including 12 in whom the HCG level was less than 1,800 mIU/ml. One woman with an early molar pregnancy had a disproportionately elevated HCG level. Correlation of sonograms with a simultaneous measurement of serum HCG level is a useful method for evaluating threatened spontaneous abortion. A disproportionately low HCG level relative to gestation sac size is evidence for an abnormal pregnancy. 相似文献
100.
This paper reports on the findings of a pilot study on reading practices in Singapore homes, which was carried out at the National Institute of Education, Singapore. A questionnaire distributed to a sample of 100 parents elicited information about the types of reading materials read at home, the person responsible for reading, the source of these materials, the importance of reading for pleasure compared to reading to learn and the languages that families read in. Results revealed that in the majority of Singaporean homes, the mother initiates reading of mostly fictional material borrowed from the public libraries. Reading aloud to children occurs in about one third of the homes, while direct instruction in reading is carried out in over two thirds of the families sampled. Reading in two languages is also perceived as an important requirement in Singapore. 相似文献