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G Cao

Publications and source records attributed to G Cao.

At least 91 records · Page 5Linked to original sources
PubMed1998

Membrane and receptor modifications of oxidative stress vulnerability in aging. Nutritional considerations.

Evidence suggests that oxidative stress (OS) may contribute to the pathogenesis of age-related decrements in neuronal function and that OS vulnerability increases as a function of age. In addition to decreased endogenous protection, increases in OS vulnerability may result from changes in membrane lipids and distribution of receptor subtype. Using a PC-12 cell model system, we have shown that H2O2 or dopamine (DA) exposure induced deficits in the cell's ability to clear (extrude/sequester, E/S) Ca2+ that are similar to those seen in aging. When plasma membrane concentrations of sphingomyelin (SPM) were used, the SPM metabolite, sphingosine-1-phosphate was increased to the same levels as those seen in aging, and enhancement of OS-induced decreases in calcium E/S following KCL depolarization was observed. Differential decreases in CA2+ E/S were also seen following DA-induced OS in COS-7 cells transfected with one of five muscarinic receptor subtypes. Cells transfected with either M1, M2, or M4 receptors showed significantly greater vulnerability to OS (as expressed by greater decrements in calcium E/S and cell death) than those transfected with M3 or M5 receptors. The vitamin E analogue, Trolox, and the nitrone-trapping agent, PBN, were not effective in altering E/S decrements but were effective in preventing cell death 24 h after OS exposure. These findings suggest that putative regional (e.g., striatum and hippocampus) increases in OS vulnerability and loss of neuronal function in aging may be dependent upon membrane SPM concentration and receptor subtype. In related studies, attempts were made to determine whether increased OS protection via nutritional increases in antioxidant levels in rats [using diets supplemented with vitamin E (500IU/kg), strawberry extracts (9.4 g/kg dried aqueous extract, DAE), spinach (6.7 g/kg DAE), or blueberry extracts (10 g/kg DEA for six weeks)] would protect against exposure to 100% O2 (a model of accelerated neuronal aging). Results indicated that these diets were effective in preventing OS-induced decrements in several parameters (e.g., nerve growth factor decreases), suggesting that although there may be increases in OS vulnerability in aging, phytochemicals present in antioxidant-rich foods may be beneficial in reducing or retarding the functional central nervous system deficits seen in aging or oxidative insult.

Aging↗
PubMed1998

The effect of long-term dietary supplementation with antioxidants.

The impact of diet and specific food groups on aging and age-associated degenerative diseases has been widely recognized in recent years. The modern concept of the free radical theory of aging takes as its basis a shift in the antioxidant/prooxidant balance that leads to increased oxidative stress, dysregulation of cellular function, and aging. In the context of this theory, antioxidants can influence the primary "intrinsic" aging process as well as several secondary age-associated pathological processes. For the latter, several epidemiological and clinical studies have revealed potential roles for dietary antioxidants in the age-associated decline of immune function and the reduction of risk of morbidity and mortality from cancer and heart disease. We reported that long-term supplementation with vitamin E enhances immune function in aged animals and elderly subjects. We have also found that the beneficial effect of vitamin E in the reduction of risk of atherosclerosis is, in part, associated with molecular modulation of the interaction of immune and endothelial cells. Even though the effects of dietary antioxidants on aging have been mostly observed in relation to age-associated diseases, the effects cannot be totally separated from those related to the intrinsic aging process. For modulation of the aging process by antioxidants, earlier reports have indicated that antioxidant feeding increased the median life span of mice to some extent. To further delineate the effect of dietary antioxidants on aging and longevity, middle-aged (18 mo) C57BL/6NIA male mice were fed ad libitum semisynthetic AIN-76 diets supplemented with different antioxidants (vitamin E, glutathione, melatonin, and strawberry extract). We found that dietary antioxidants had no effect on the pathological outcome or on mean and maximum life span of the mice, which was observed despite the reduced level of lipid peroxidation products, 4-hydroxynonenol, in the liver of animals supplemented with vitamin E and strawberry extract (1.34 +/- 0.4 and 1.6 +/- 0.5 nmol/g, respectively) compared to animals fed the control diet (2.35 +/- 1.4 nmol/g). However, vitamin E-supplemented mice had significantly lower lung viral levels following influenza infection, a viral challenge associated with oxidative stress. These and other observations indicate that, at present, the effects of dietary antioxidants are mainly demonstrated in connection with age-associated diseases in which oxidative stress appears to be intimately involved. Further studies are needed to determine the effect of antioxidant supplementation on longevity in the context of moderate caloric restriction.

Aging↗
PubMed1998

Comparison of carcinoembryonic antigen promoter regions isolated from human colorectal carcinoma and normal adjacent mucosa to induce strong tumor-selective gene expression.

To establish in vivo gene therapy against cancer, it is requisite to induce strong, cancer cell-selective expression of a therapeutic gene. Comparison of the promoter activity of 5' flanking regions of the carcinoembryonic antigen (CEA) gene isolated from various origins is therefore of considerable interest. The 5' flanking region of the CEA gene between -135 and +69 bp upstream from the transcriptional start site, which is recognized as the core promoter region, was isolated from CEA-producing human colorectal carcinoma (CRC), normal adjacent mucosa, CEA-producing cell lines and CEA-non-producing cell lines. No mutations were observed by single-strand conformation polymorphism in the CEA promoter regions. Subsequent sequence analysis revealed that there were no mutations in the CEA promoter regions isolated from CEA-producing CRC and normal adjacent mucosa. Furthermore, nuclear extracts prepared from CEA-producing human CRC cells could equally bind to both the CEA promoter fragments isolated from CEA-producing CRC and normal mucosa. Both CEA promoter regions could direct 5- to 20-fold higher expression of a luciferase reporter gene in CEA-producing cells than in CEA-non-producing cells. Therefore, we suggest that the use of either CEA promoter region isolated from CRC or normal mucosa is equally effective to induce strong, CEA-producing cancer-selective expression of a therapeutic gene.

Base Sequence↗
PubMed1998

Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits.

Recent research has indicated that increased vulnerability to oxidative stress may be the major factor involved in CNS functional declines in aging and age-related neurodegenerative diseases, and that antioxidants, e.g., vitamin E, may ameliorate or prevent these declines. Present studies examined whether long-term feeding of Fischer 344 rats, beginning when the rats were 6 months of age and continuing for 8 months, with diets supplemented with a fruit or vegetable extract identified as being high in antioxidant activity, could prevent the age-related induction of receptor-mediated signal transduction deficits that might have a behavioral component. Thus, the following parameters were examined: (1) oxotremorine-enhanced striatal dopamine release (OX-K+-ERDA), (2) cerebellar beta receptor augmentation of GABA responding, (3) striatal synaptosomal 45Ca2+ clearance, (4) carbachol-stimulated GTPase activity, and (5) Morris water maze performance. The rats were given control diets or those supplemented with strawberry extracts (SE), 9.5 gm/kg dried aqueous extract (DAE), spinach (SPN 6.4 gm/kg DAE), or vitamin E (500 IU/kg). Results indicated that SPN-fed rats demonstrated the greatest retardation of age-effects on all parameters except GTPase activity, on which SE had the greatest effect, whereas SE and vitamin E showed significant but equal protection against these age-induced deficits on the other parameters. For example, OX-K+-ERDA enhancement was four times greater in the SPN group than in controls. Thus, phytochemicals present in antioxidant-rich foods such as spinach may be beneficial in retarding functional age-related CNS and cognitive behavioral deficits and, perhaps, may have some benefit in neurodegenerative disease.

Aging↗
PubMed1998

Disease incidence and longevity are unaltered by dietary antioxidant supplementation initiated during middle age in C57BL/6 mice.

The ability of augmented antioxidant consumption to alter disease incidence, lesion burden and/or longevity was studied in adult male C57BL/6 mice. Mice were fed modified AIN76 diet or modified AIN76 supplemented with vitamin E, glutathione (GSH), vitamin E and GSH, melatonin or strawberry extract starting at 18 months of age. All the mice in this study were heavier than reference populations of male C57BL/6 mice fed NIH-07 or NIH-31, which were maintained without a mid-life change in diet. Fatty liver, focal kidney atrophy and proteinacious casts in the renal tubules were observed more frequently in this study population than in the reference populations. Lesion burden and incidence of specific lesions observed amongst the various groups in this study did not differ. There were no differences observed for longevity of any of the study groups. The longevity observed in this study was similar to that previously reported for male C57BL/6 mice. Thus, diet supplementation with antioxidants initiated during middle age did not appear to affect age-associated lesions patterns, lesion burden or longevity for ad libitum fed male C57BL/6 mice.

Aging↗
PubMed1998

Pharmacokinetic interactions between two human immunodeficiency virus protease inhibitors, ritonavir and saquinavir.

OBJECTIVE: To assess the pharmacokinetic interaction between ritonavir and saquinavir. METHODS: Ritonavir and saquinavir were administered in single doses to six groups of healthy volunteers in a two-way (saquinavir alone and ritonavir plus saquinavir for groups I through V) and a three-way (ritonavir alone, saquinavir alone, and ritonavir plus saquinavir for group VI) crossover manner with the following doses: group I, 200 mg saquinavir and 300 mg ritonavir; group II, 200 mg saquinavir and 600 mg ritonavir; group III, 400 mg saquinavir and 300 mg ritonavir; group IV, 400 mg saquinavir and 600 mg ritonavir; group V; 600 mg saquinavir and 200 mg ritonavir; group VI, 600 mg saquinavir and 600 mg ritonavir. RESULTS: Coadministration of ritonavir markedly increased the area under the plasma concentration-time curve (AUC) and peak concentration of saquinavir (> 50-fold and 22-fold, respectively). For a constant ritonavir dose, the pharmacokinetics of saquinavir were relatively proportional to dose. For a constant saquinavir dose, the increase in saquinavir concentration tended to be less than proportional to ritonavir dose. Ritonavir reduced intersubject variability in the saquinavir AUC from 60% to 28%. The in vivo inhibition constant was 0.025 +/- 0.020 micrograms/ml with noncompartmental estimation and 0.0164 +/- 0.0004 micrograms/ml with nonlinear mixed-effects model compartmental analysis. Saquinavir showed no clinically significant effect on the pharmacokinetics of ritonavir (+6.4% in AUC). The regimens were well tolerated. CONCLUSIONS: The large effect of ritonavir on the pharmacokinetics of saquinavir is consistent with a large reduction of saquinavir first-pass metabolism and postabsorptive clearance. Given the limited bioavailability of saquinavir given in the hard gelatin capsule formulation, this drug interaction is expected to have implications in the use of protease inhibitors in the management of human immunodeficiency virus infection.

Adult↗
PubMed1998

Age-related neurodegeneration and oxidative stress: putative nutritional intervention.

This review describes age-related changes that occur in neuronal function and cites evidence to show that these alterations may be the result of increased sensitivity to oxidative stress (OS). Evidence is presented to show that the abilities to mitigate the OS effects and to repair the damage from OS show decline as a function of age. Results from age- and OS-sensitive tests are given; these results indicate that one of the major sites of action of OS is the membranes, especially if compromised by high amounts of sphingomyelin, and one of the major effects of OS is to further alter the calcium disregulation in aging. It is suggested that attempts to increase antioxidant protection through diets comprised of fruits and vegetables identified as being high in total antioxidant activity might prevent or reverse the deleterious OS effects on neuronal aging.

Aging↗
PubMed1998

Increases in human plasma antioxidant capacity after consumption of controlled diets high in fruit and vegetables.

BACKGROUND: The putative beneficial effects of an increased consumption of fruit and vegetables have been associated with antioxidant nutrients. However, the effect of fruit and vegetable consumption on the overall antioxidant status in humans is unclear. OBJECTIVE: The objective of this study was to investigate whether a diet rich in fruit and vegetables would affect the antioxidant capacity of human plasma. DESIGN: Thirty-six healthy nonsmokers resided in a metabolic research unit and consumed 2 sets of controlled diets. Diet A contained 10 servings of fruit and vegetables each day for 15 d. Diet B was the same as diet A, except diet B also provided 2 servings of broccoli each day on days 6-10. There was a free-living period of a minimum of 6 wk between the 2 experiments using either diet A or diet B. Fasting plasma antioxidant capacity, measured as oxygen radical absorbance capacity (ORAC), and alpha-tocopherol concentrations were determined on days 1, 6, 11, and 16. RESULTS: The fasting baseline plasma ORAC of these subjects was significantly correlated with their estimated daily intake of total antioxidants from fruit and vegetables during the previous year. Plasma ORAC of these subjects was significantly increased by both diets A and B. This increase in ORAC could not be explained by the increase in the plasma alpha-tocopherol concentration. CONCLUSION: Increased consumption of fruit and vegetables can increase the plasma antioxidant capacity in humans.

Adult↗
PubMed1998

Serum antioxidant capacity is increased by consumption of strawberries, spinach, red wine or vitamin C in elderly women.

It is often assumed that antioxidant nutrients contribute to the protection afforded by fruits, vegetables, and red wine against diseases of aging. However, the effect of fruit, vegetable and red wine consumption on the overall antioxidant status in human is unclear. In this study we investigated the responses in serum total antioxidant capacity following comsumption of strawberries (240 g), spinach (294 g), red wine (300 ml) or vitamin C (1250 mg) in eight elderly women. Total antioxidant capacity was determined using different methods: oxygen radical absorbance capacity (ORAC) assay, Trolox equivalent antioxidant capacity (TEAC) assay and ferric reducing ability (FRAP) assay. The results showed that the total antioxidant capacity of serum determined as ORAC, TEAC and FRAP, using the area under the curve, increased significantly by 7-25% during the 4-h period following consumption of red wine, strawberries, vitamin C or spinach. The total antioxidant capacity of urine determined as ORAC increased (P < 0.05) by 9.6, 27.5, and 44.9% for strawberries, spinach, and vitamin C, respectively, during the 24-h period following these treatments. The plasma vitamin C level after the strawberry drink, and the serum urate level after the strawberry and spinach treatments, also increased significantly. However, the increased vitamin C and urate levels could not fully account for the increased total antioxidant capacity in serum following the consumption of strawberries, spinach or red wine. We conclude that the consumption of strawberries, spinach or red wine, which are rich in antioxidant phenolic compounds, can increase the serum antioxidant capacity in humans. J. Nutr. 2383-2390, 1998

Aged↗
PubMed1998

Postprandial plasma carotenoid responses following consumption of strawberries, red wine, vitamin C or spinach by elderly women.

This study investigated the postprandial plasma responses of carotenoids for 24 h after feeding five specific breakfast beverages; four of which had low or no carotenoid content. In seven fasting healthy elderly female subjects a blood sample (baseline) was obtained, after which they were given a breakfast beverage, containing one of the following: 1) strawberries (240 g); 2) ascorbic acid (1250 mg); 3) spinach (294 g); 4) red wine (300 mL); and 5) control (breakfast beverage only). Blood samples were collected at 0.5, 1, 4, 7, 11, 15 and 24 h. Plasma carotenoids were measured using HPLC. No significant differences were found in the levels of the plasma carotenoids measured among the various treatments at baseline. In the spinach treatment, plasma lutein, zeaxanthin and beta-carotene levels at 7, 11, 15 and 24 h were significantly higher than those at baseline, as expected. All of the carotenoids measured in the control and vitamin C treatments, at subsequent sampling times were not significantly different from those at baseline. However, for most carotenoids, strawberry and red wine feeding resulted in significantly lower carotenoids values from baseline at 11 and 15 h. Subjects who received a diet with low levels of carotenoids, but whose postprandial plasma levels of carotenoids remain steady, might be explained by a mechanism that promotes secretion of carotenoids into the circulation. Assuming that plasma carotenoids are being used over time, we hypothesize that strawberries and red wine contain some substances that interfere with the secretion of carotenoids into the circulation.

Aged↗
PubMed1998

Pharmacokinetic interaction between ritonavir and indinavir in healthy volunteers.

The pharmacokinetic interaction between indinavir and ritonavir was evaluated in five groups of healthy adult volunteers to explore the potential for twice-daily (b.i.d.) dosing of this combination. All subjects received 800 mg of indinavir every 8 h (q8h) on day 2. In addition, subjects in group I received one dose of 800 mg of indinavir on day 1 and 800 mg of indinavir q8h on day 17. Subjects in Groups II and IV each received one dose of 600 mg of indinavir on days 1 and 17, and subjects in groups III and V each received one dose of 400 mg of indinavir on days 1 and 17. During days 3 to 17, ritonavir placebo or ritonavir at 200, 300, 300, or 400 mg q12h was given to groups I, II, III, IV, and V, respectively. Ritonavir at steady state probably inhibited the cytochrome P-450 3A metabolism of indinavir and substantially increased plasma indinavir concentrations, with the area under the plasma concentration-time curve (AUC) increasing up to 475% and the peak concentration in serum (Cmax) increasing up to 110%. The Cmax/trough concentration ratio decreased from 50 in standard q8h regimens to less than 14 when indinavir was administered with ritonavir. For a constant indinavir dose, an increase in the ritonavir dose yielded similar indinavir AUCs, Cmaxs, and concentrations at 12 h (C12s). For a constant ritonavir dose, an increase in the indinavir dose resulted in approximately proportional increases in the indinavir AUC, less than proportional increases in Cmax, and slightly more than proportional increases in C12. Ritonavir reduced between-subject variability in the indinavir AUC and trough concentrations and did not affect indinavir renal clearance. With the altered pharmacokinetic profile, indinavir likely could be given as a b.i.d. combination regimen with ritonavir. This could potentially improve patient compliance and thereby reduce treatment failures.

Adolescent↗
PubMed1998

Mortality patterns among adult Hispanics: findings from the NHIS, 1986 to 1990.

OBJECTIVES: The purpose of this study was to assess the mortality pattern of the adult Hispanic population in the United States. METHODS: This was a cohort study using data from the National Health Interview Survey from 1986 through 1990. Deaths were ascertained by matching the National Death Index through 1991. RESULTS: This representative national sample included 297,640 non-Hispanic Whites, 53,552 Blacks, and 27,239 Hispanics, all aged 18 years or older at baseline. Different matching criteria resulted in modest differential estimates of the number of deaths by ethnic groups; these differences were quantitatively more important for Hispanics. Overall age-standardized mortality was lower among Hispanics. A prominent age by race interaction was apparent. The Hispanic: White mortality ratio was 1.33, 0.92, and 0.76 among men aged 18 through 44, 45 through 64, and 65 and older, respectively. Among women in the same age groups the Hispanic: White mortality ratio was 1.22, 0.75, and 0.70, respectively. CONCLUSIONS: Longitudinal cohorts provide an important source of health status information on Hispanics. These results suggest that overall mortality is lower among Hispanics than among non-Hispanic Whites, especially in the oldest age group. Among younger and middle-aged persons, the mortality of Hispanics is similar to or even higher than that of Whites.

Adult↗
PubMed1998

[Enhancement of Vp16 inducing apoptosis of leukemic cells by retrovirus-mediated bcl-2 anti-sense RNA].

OBJECTIVE: To explore the effects of retrovirus-mediated bcl-2 antisense RNA on apoptosis of leukemic cells. METHODS: Retrovirus was packaged in vitro with PA317 cells and Jurkat cell was transducted with collected virus; The expressions of bcl-2 mRNA and protein were assayed by RT-PCR and Western blotting, respectively. Apoptosis was assayed by flow cytometry and DNA "ladder". RESULTS: Expression of intrinsic bcl-2 was decreased, and the sensitivity of leukemic cells to Vp16 and the apoptosis of leukemic cells line Jurkat cells were enhanced by transfected bcl-2 antisense RNA. CONCLUSION: Antisense bcl-2 enhances Vp16 inducing apoptosis of leukemic cells. The results provide a useful experimental basis for leukemia therapy.

Antineoplastic Agents, Phytogenic↗
PubMed1998

[Enhancement of apoptotic sensitivity induced by UV irradiation on the p53-transducted K562 cells].

OBJECTIVE: To answer whether wild-type p53 can sensitize K562 cell apoptosis induced by UV irradiation. METHODS: K562 cells transducted with retrovirus encoding wild-type p53 were irradiated by ultraviolet for different time and then cultured for different time. Apoptosis was detected by TDT end labelling technique, DNA fragmentation and MTT assay. RESULTS: TDT end labelling and DNA fragmentation showed that apoptosis induced by 8 min UV-irradiation differed significantly between K562-neo and K562-p53 cells. CONCLUSION: Wild-type p53 can enhance apoptosis induced by UV-irradiation on K562 cells.

Apoptosis↗
PubMed1998

[A comparative study on transabdominal versus retroperitoneal approach for abdominal aortic surgery].

OBJECTIVE: To retrospectively compare transabdominal with retroperitoneal approach to the aorta for infrarenal aortic reconstruction. METHODS: From January 1988 to December 1996, Patients undergoing surgery for abdominal aortic aneurysm (AAA) or aortoiliac occlusive disease (AIOD) were included in the retrospective comparison of transabdominal approach (TAA) with retroperitoneal approach (RPA) for aortic surgery. Forty-four patients were analyzed, with 26 (23 with AAA and 3 with AIOD) in TAA group and 18 (16 with AAA and 2 with AIOD) in RPA group. There were no significant differences between the groups in terms of age, sex, comorbid conditions, and vascular graft anastomoses. RESULTS: The incidence of intraoperative complications was similar for both groups. Postoperatively, RPA group had significantly fewer overall complications than TAA group (P < 0.01). The incidence of prolonged ileus (6 cases in TAA group, none in RPA group) and small bowel obstruction (2 cases in TAA group, none in RPA group) was higher in the TAA group (P < 0.01). Postoperatively four deaths occurred with two in each group. There was no difference in pulmonary complications (P = 0.70). In long-term follow-up (mean 32 months), no significant difference was found in incisional hernias in the two groups. CONCLUSIONS: RPA approach, with fewer postoperative complications, short stay in the hospital and intensive care unit, is a safer and simpler approach for abdominal aortic surgery.

Aged↗
PubMed1998

[Endovascular exclusion of abdominal aortic aneurysm].

OBJECTIVE: To explore the indications, methods, manipulations, and problems of endovascular exclusion of abdominal aortic aneurysm (AAA). METHOD: Under general anesthesia and dynamic supervision of DSA, an endovascular exclusion with a stent-graft complex of 11.0 cm x 2.6 cm was successfully performed on a 70-year-old man contraindicated for major open surgery with AAA of 10.0 cm x 6.0 cm and an AAA neck of 2.5 cm x 1.6 cm. RESULT: The patient was up and about on the first postoperative day. Duplex scan (by the end of the first postoperative week) and CT (on the postoperative 20th day) revealed a completely excluded AAA by the stent-graft that was patent and had an inner diameter of 2.2-2.4 cm, without migration and torsion. The primary AAA sac was full of thrombi and no patent lumbar and inferior mesenteric arteries were observed. The external diameter of AAA was unchanged, renal and iliac arteries were all patent, but a micro-crevice between the proximal end of the stent-graft and the anterior wall of the AAA neck was revealed. Six months postoperative follow-up showed that the patient's abdominal pulsatile mass and the left lower extremity's claudication disappeared. CONCLUSION: Endovascular exclusion of AAA is of great practical value.

Aged↗
PubMed1998

Lack of CYP3A inhibition effects of sertindole on terfenadine in healthy volunteers.

The effect of sertindole (a new selective antipsychotic compound) on the pharmacokinetic disposition of terfenadine was investigated. Thirteen subjects who completed the study received a single 120 mg dose of terfenadine alone or with concomitant 20 mg sertindole daily. The mean values for terfenadine Cmax (alone: 2.42 +/- 1.48 ng/ml, in combination: 2.99 +/- 1.85 ng/ml) and AUC (29.6 +/- 18.9 vs 37.9 +/- 23.4 ng x hr/ml) did not change statistically significant in the presence of sertindole (p > 0.05). Similarly, the mean Cmax (531 +/- 195 vs 506 +/- 190 ng/ml) and AUC (3,728 +/- 1,163 vs 4,003 +/- 1,739 ng x hr/ml) values of carboxyterfenadine did not change statistically significant in the presence of sertindole (p > 0.05). The other pharmacokinetic parameters of terfenadine and carboxyterfenadine such as Tmax, t1/2, as well as the carboxyterfenadine to terfenadine Cmax and AUC ratios did not change in the presence of sertindole. Although terfenadine is a substrate for CYP3A (cytochrome P-450 3A), while sertindole is a substrate for both CYP2D6 and CYP3A4, the results in this study suggest that sertindole, at a clinical dose, is not an inhibitor of the metabolism of terfenadine.

Absorption↗