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At least 433 records · Page 24Linked to original sources
PubMed2005

Activation of dopaminergic neurotransmission in the medial prefrontal cortex by N-methyl-d-aspartate stimulation of the ventral hippocampus in rats.

Many behavioral functions-including sensorimotor, attentional, memory, and emotional processes-have been associated with hippocampal processes and with dopamine transmission in the medial prefrontal cortex (mPFC). This suggests a functional interaction between hippocampus and prefrontal dopamine. The anatomical substrate for such an interaction is the intimate interconnection between the ventral hippocampus and the dopamine innervation of the mPFC. The present study yielded direct neurochemical evidence for an interaction between ventral hippocampus and prefrontal dopamine transmission in rats by demonstrating that subconvulsive stimulation of the ventral hippocampus with N-methyl-d-aspartate (NMDA; 0.5 mug/side) activates dopamine transmission in the mPFC. Postmortem measurements revealed that bilateral NMDA stimulation of the ventral hippocampus, resulting in locomotor hyperactivity, increased the homovanillic acid/dopamine ratio, an index of dopamine transmission, in the mPFC; indices of dopamine transmission in any of five additionally examined forebrain regions (amygdala, nucleus accumbens shell/core, lateral prefrontal cortex, caudate putamen) were unaltered. In vivo microdialysis measurements in freely moving rats corroborated the suggested activation of prefrontal dopamine transmission by demonstrating that unilateral NMDA stimulation of the ventral hippocampus increased extracellular dopamine in the ipsilateral mPFC. The suggested influence of the ventral hippocampus on prefrontal dopamine may be an important mechanism for hippocampo-prefrontal interactions in normal behavioral processes. Moreover, it indicates that aberrant hippocampal activity, as found in neuropsychiatric diseases, such as schizophrenia and mood disorders, may contribute to disruption of certain cognitive and emotional functions which are extremely sensitive to imbalanced prefrontal dopamine transmission.

Animals↗
PubMed2005

Maternal knowledge, attitude and practice on folic acid intake among Arabian Qatari women.

BACKGROUND: Periconceptional folic acid supplementation is effective in preventing primary and secondary neural tube defects (NTDs) and other congenital defects. It is important to estimate folate intake and knowledge in women of child-bearing age, in relation to risk of congenital anomalies. AIM: The aim of this study was to determine the level of knowledge about the usefulness of periconceptional folic acid supplementation in a sample of women in the child-bearing age. DESIGN: This is a cross-sectional survey. SETTING: Eleven primary health care centers and women's hospital in Qatar. SUBJECTS: A multistage sampling design was used and a representative sample of 1,800 Qatari women aged between 18 and 45 years were surveyed during the period June to November 2004. One thousand four hundred and eighty women (82.2%) expressed their consent to participate in this study. METHODS: A confidential, anonymous questionnaire was completed by the selected subjects assessing folic acid awareness. Questionnaires were administered to women who were seeking routine antenatal care at health centers and Women's Hospital. Questions covered knowledge and use of folic acid supplements, pregnancy intention, and demographic and socioeconomic characteristics. Factors affecting study outcomes were examined individually by computing crude odd ratios and adjusted for other covariates using unconditional logistic regression. RESULTS: Out of 1480 women surveyed, 53.7% of them reported that they heard of folate. Of these, only half of the subjects knew that folate was something important. Overall, 20.3% of the respondents took folic acid. The most common information sources on folate were physicians (63.4%), and newspapers/magazine/books (21.7%). From those who heard of folate, only 14% knew that it can prevent birth defects. 40.6% of the subjects who heard folate were aware that green leafy vegetables were fortified with folic acid. In univariate analysis, awareness of folic acid was significantly associated with education of mother. Again, higher educated women (41.3%) knew more about folic acid and used it more often in the periconceptional and first trimester period. CONCLUSION: Awareness and use of folic acid was less prevalent among Qatari women. Educated women were aware of the importance of the intake of folic acid. The study findings suggested possible avenue for intervention to increase awareness and intake of folic acid.

Adult↗
PubMed2005

Altered antioxidant status in peripheral skeletal muscle of patients with COPD.

Despite the growing field of interest in the role of pulmonary oxidative stress in chronic obstructive pulmonary disease (COPD), barely any data are available with respect to antioxidant capacity in the peripheral musculature of these patients. The main objective of this study was to assess in detail the antioxidant status in skeletal muscle of patients with COPD. Biopsies from the vastus lateralis of 21 patients with COPD and 12 healthy age-matched controls were analysed. Total antioxidant capacity, vitamin E, glutathione, and uric acid levels were determined and the enzyme activities of superoxide dismutase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase were measured. Malondialdehyde was measured as an index of lipid peroxidation. The total antioxidant capacity and the uric acid levels were markedly higher in COPD patients than in healthy controls (25%, P = 0.006 and 24%, P = 0.029, respectively). Glutathione-S-transferase activity was also increased (35%; P = 0.044) in patients compared to healthy subjects. Vitamin E level was lower in patients than in controls (P < 0.05). The malondialdehyde level was not different between the two groups. It can be concluded that the muscle total antioxidant capacity is increased in patients with COPD. Together with the reduced vitamin E levels, the increased glutathione-S-transferase activity and normal levels of lipid peroxidation products, these findings suggest that the antioxidant system may be exposed to and subsequently triggered by elevated levels of reactive oxygen species.

Aged↗
PubMed2004

Fertility is reduced after restorative proctocolectomy with ileal pouch anal anastomosis: a study of 300 patients.

BACKGROUND: Restorative proctocolectomy and ileal pouch anal anastomosis (RP/IPAA) has become the gold standard surgical therapy for the majority of patients with mucosal ulcerative colitis and familial adenomatous polyposis. The aims of this study were to evaluate the fertility rates before and after RP/IPAA, to compare them with the reproductive data of the general United States population, and to determine surgical parameters that might influence subsequent fertility. METHODS: Three hundred women of reproductive age who underwent RP/IPAA between 1983 and 2001 completed a mailed questionnaire regarding their reproductive function before and after the procedure. Additional information was obtained from the pelvic pouch database. The reproductive information was compared to age-matched historical control subjects from the United States general population. The associations between changes in fertility and surgical parameters were also investigated. RESULTS: The median (25th, 75th percentile) age at surgery was 28 (24, 33) years. Out of 300 women, 206 attempted to conceive. Before operation, 48 (38%) of 127 patients were unsuccessful after 1 year of unprotected intercourse, whereas after operation, 76 (56%) of 135 patients were unsuccessful. This infertility rate was higher after operation than before (P <.001). For the subgroup of 56 women who tried to get pregnant both before and after operation, the infertility rate was higher after operation than before (69% vs 46%; P=.005). Also, a higher percentage of these patients who had an intraoperative transfusion were infertile after operation compared to patients who did not have an intraoperative transfusion (54% vs 21%; P=.023). CONCLUSIONS: There was an increase in the infertility rate after RP/IPAA. Intraoperative blood transfusion had a negative impact on the fertility rate after operation in patients who tried to conceive both before and after RP/IPAA.

Adolescent↗
PubMed2004

Lecithinized copper,zinc-superoxide dismutase as a protector against doxorubicin-induced cardiotoxicity in mice.

Production of superoxide radicals from doxorubicin is widely accepted to be the cause of the cardiotoxicity induced by this antitumor agent. Pretreatment with superoxide dismutase could improve the therapeutic application. Aim of the present study was to determine whether lecithinized superoxide dismutase (PC-SOD) can serve as a cardioprotective drug during doxorubicin treatment. The protective potential of PC-SOD on doxorubicin-induced cardiotoxicity was investigated in BALB/c mice. The possible influence of PC-SOD on the antitumor activity of doxorubicin was investigated in vitro as well as in vivo. Mice were treated intravenously with doxorubicin (4 mg x kg(-1)) or doxorubicin and PC-SOD (5000, 20000 or 80000 U x kg(-1)) weekly x 6 and appropriate controls were included. Cardiotoxicity was monitored for 8 weeks by ECG measurement. The influence of PC-SOD on the antitumor activity of doxorubicin was evaluated in three human malignant cell lines. Nude mice bearing OVCAR-3 human ovarian cancer xenografts were treated intravenously with doxorubicin (8 mg x kg(-1)) alone or preceded by PC-SOD 20000 or 80000 U x kg(-1) weekly x 2 and appropriate controls were included. PC-SOD prevented doxorubicin-induced cardiotoxicity already at 5000 U x kg(-1) whereas 20000 and 80000 U x kg(-1) were equally protective. No toxicity was observed in mice treated with PC-SOD. PC-SOD did not interfere with the antiproliferative effects of doxorubicin in vitro. In vivo, PC-SOD had no negative effect on the inhibition of xenograft growth induced by doxorubicin. It can be concluded that PC-SOD protects the heart, but not the tumor against doxorubicin. These data suggest that PC-SOD may be a suitable cardioprotector during doxorubicin treatment.

Animals↗
PubMed2005

Pro-apoptotic effects of the flavonoid luteolin in rat H4IIE cells.

Polyphenols are ubiquitous substances in the diet. Their anti-oxidative, anti-inflammatory and anti-viral effects are of interest for human health, and polyphenols such as luteolin are used at high concentrations in food supplements. The aim of this project was to determine the intrinsic effects of luteolin in H4IIE rat hepatoma cells. Luteolin is relatively toxic, cell death was caused via induction of apoptosis as detected by DNA-ladder formation, by nuclear fragmentation and activation of apoptotic enzymes (caspase-2, -3/7, -9 and -8/10). Luteolin (250 microM, 24 h) increased the caspase-3/7 activity four-fold and the caspase-9 activity six-fold. In a time course experiment caspase-9 is activated after 6h, while caspase-2 and -3/7 are activated after 12 h. After 24 h, caspase-8/10 also displays activation. We found a concentration-dependent increase in malondialdehyde release suggesting a prooxidative effect of luteolin. Furthermore, we analysed DNA strand break formation by luteolin and found a distinct increase of DNA strand breaks after incubation for 3h with 100 microM luteolin, a concentration which induces oligonucleosomal DNA cleavage at 24h. In conclusion, the sequence of events is compatible with the assumption that luteolin triggers the mitochondrial pathway of apoptosis, probably by inducing DNA damage.

Animals↗
PubMed2004

The thiol reactivity of the oxidation product of 3,5,7-trihydroxy-4H-chromen-4-one containing flavonoids.

Flavonoids are assumed to have beneficial effects due to their antioxidant properties. The catechol moiety present in numerous flavonoids is oxidized during the antioxidative reaction yielding a quinone. Quinones are toxic due to their ability to react, e.g. with thiol groups. The 3,5,7-trihydroxy-4H-chromen-4-one group is another antioxidant pharmacophor in certain flavonoids. During the antioxidative reaction this group is also oxidized. The aim of the present study is to determine the thiol reactivity of this oxidized group. Galangin is a flavonoid that only contains the 3,5,7-trihydroxy-4H-chromen-4-one group as the antioxidant pharmacophor. Incubation of galangin with horseradish peroxidase/H(2)O(2) leads to an oxidation product which after addition of glutathione is instantaneously converted to an adduct. Based on these results it is expected that--similar to the catechol containing antioxidants--the 3,5,7-trihydroxy-4H-chromen-4-one containing antioxidants shift the damage provoked by oxidative stress from lipid peroxidation to thiol arylation. This should be considered in application of these types of antioxidants.

Animals↗
PubMed2005

Galangin protects pig detrusor nerves from repetitive field stimulation and anoxia/glucopenia injury.

OBJECTIVES: To test the capability of the flavonoid galangin to protect pig urinary bladder from damage due to a period of repetitive field stimulation as well as a period of anoxia/glucopenia and reperfusion. METHODS: Smooth muscle strips of the pig bladder were mounted for tension recording in small organ baths and the strips underwent either 1.5 hours of repetitive field stimulation at 32 Hz for 15 seconds every 5 minutes or under anoxia/glucopenia and reperfusion conditions. Galangin, at different concentrations, was added to the reperfusion Krebs solution to check the effect of this flavonoid compared with untreated strips under the same conditions. A group of experiments was performed to examine its possible underlying mechanisms. RESULTS: Repetitive field stimulation for 1.5 hours caused a progressive decrease in the maximal contractile response to electrical field stimulation (34% decrease). Galangin (10(-7) M) partially prevented the progressive decrease in the contractile response. This effect was significantly reduced when verapamil was added to the solution. Galangin significantly improved the response of strips to electrical field stimulation under anoxia/glucopenia and reperfusion conditions compared with untreated tissues. CONCLUSIONS: Galangin has a protective effect on bladder contractility by an action that at least, in part, depends on l-type calcium channels. Furthermore, galangin protects detrusor nerves against the anoxia/glucopenic and reperfusion damage.

Animals↗
PubMed2004

Effect of interstitial stereotactic radiosurgery on behavior and subjective handicap of epilepsy in patients with gelastic epilepsy.

Patients with symptomatic epilepsy due to hypothalamic hamartomas often are compromised not only by pharmacoresistant epileptic seizures but also by behavioral disturbances and cognitive dysfunction. We report the effect of successful treatment with stereotactic interstitial radiosurgery by intrahypothalamic implantation of 125I seeds on behavior and subjective handicap. In all patients rendered seizure-free or suffering only from auras, improvement of behavior was reported by parents and colleagues or schoolteachers. Parents' ratings according to the Child Behavior Checklist showed improvements with respect to social problems and attention. Self-ratings of quality of life by adult patients showed improvements in activities, working situation, and self-perception. These improvements were not observed in patients in whom clinically manifest seizures and interictal EEG discharges persisted after radiosurgery.

Activities of Daily Living↗
PubMed2005

In vitro model of normal, immortalized ovarian surface epithelial and ovarian cancer cells for chemoprevention of ovarian cancer.

BACKGROUND: Epithelial ovarian cancer has the highest mortality rate among the gynecologic cancers. The synthetic retinoid, N-(4-hydroxyphenyl) retinamide (4-HPR), has been used in the chemoprevention of ovarian cancer. However, the effectiveness of its application for different populations has been questioned because of the genetic differences among normal, high risk, and women with cancer. OBJECTIVE: To explore the similarities and the differences in 4-HPR effects on different ovarian epithelial cells which mimic different populations of women, normal ovarian surface epithelium to represent the normal population of women, immortalized ovarian surface epithelium to represent premalignant changes, and cells derived from ovarian cancer cells to represent malignant changes were used as in vitro models. METHODS: Normal ovarian surface epithelial cells, immortalized ovarian surface epithelial cells, and ovarian cancer cells were incubated for different intervals with increasing concentrations of 4-HPR. Growth inhibition, the fraction of apoptotic cells, the expression of apoptosis-related genes, including p53, p16, p21, and caspase-3, and mitochondrial permeability transition were measured before and after 4-HPR treatment. RESULTS: Treatment with 4-HPR produced growth inhibition and apoptosis in a dose-dependent manner for all 3 cell types. 4-HPR produced the strongest activation of the p53 pathway in normal ovarian epithelial (NOE) cells, while it caused the largest increase in MPT in the cancer cells, suggesting a different mechanism for growth inhibition and/or apoptosis in these cell lines. 4-HPR, at a concentration of 10 muM, had a maximal effect on caspase-3 activity at 72 h in normal cells and at 48 h in immortalized and cancer cells, although the effects were modest. CONCLUSIONS: Normal ovarian surface epithelial cells, immortalized ovarian surface epithelial cells, and ovarian cancer cells showed a differential response to 4-HPR. Although the same endpoints of growth inhibition and apoptosis induction were present in response to 4-HPR, these endpoints may be regulated through different pathways. IMPLICATIONS: Clinical trials with higher concentrations of 4-HPR should prove beneficial.

Anticarcinogenic Agents↗
PubMed2005

Potential markers that complement expression of CA125 in epithelial ovarian cancer.

BACKGROUND: When ovarian carcinoma is diagnosed in stage I, up to 90% of patients can be cured with surgery and currently available chemotherapy. At present, less than 25% of cases are diagnosed at this stage. To increase the fraction of ovarian cancers detected at an early stage, screening strategies have been devised that utilize a rising serum CA125 level to trigger the performance of transvaginal sonography. One limitation of CA125 as an initial step in such a screening strategy is that up to 20% of ovarian cancers lack expression of the antigen. Serum tumor markers that can be detected in ovarian cancers that lack CA125 expression might improve the sensitivity for early detection. METHODS: From 296 ovarian cancers, 65 (22%) were found to have weak or absent CA125 expression on immunoperoxidase staining. Tissue expression of CA125 was compared to serum CA125 levels. Using immunoperoxidase staining of tissue arrays, we have assessed expression of 10 potential serum tumor markers in the 65 epithelial ovarian cancers with little or no CA125 expression and in ovarian cystadenomas, tumors of low malignant potential, normal ovaries, and 16 other normal tissues. RESULTS: Low or absent expression of CA125 in surgical specimens of epithelial ovarian cancer was associated with low levels of serum CA125 in pre-operative serum specimens. In ovarian cancers that lacked CA125, all specimens (100%) expressed human kallikrein 10 (HK10), human kallikrein 6 (HK6), osteopontin (OPN), and claudin 3. A smaller fraction of CA125-deficient ovarian cancers expressed DF3 (95%), vascular endothelial growth factor (VEGF) (81%), MUC1 (62%), mesothelin (MES) (34%), HE4 (32%), and CA19-9 (29%). When reactivity with normal tissues was considered, however, MES and HE4 showed the greatest specificity. Differential expression was also found for HK10, OPN, DF3, and MUC1. CONCLUSIONS: At the level of tissue expression, each of 10 potential serum markers could be detected in 29-100% of ovarian cancers that had low or absent expression of CA125. Several markers exhibited more intense expression in cancers than in normal organs. Further investigation is needed to demonstrate complementary expression of markers in serum.

Antigens↗
PubMed1991

Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. I. Correlation of receptor expression with prognostic factors in patients with ovarian cancer.

Previous studies in breast and bladder cancer have suggested that epidermal growth factor receptor is expressed by only a proportion of cancers and is associated with poor clinical outcome. We used a monoclonal antibody specifically reactive with the extracellular domain of the epidermal growth factor receptor to localize this receptor immunohistochemically in frozen sections of normal ovary and epithelial ovarian cancer. Normal ovarian epithelium was found to express epidermal growth factor receptor in all cases. Among 87 ovarian cancers, however, 23% did not express immunohistochemically detectable receptor. Epidermal growth factor receptor expression was not related to histologic grade or stage, but was associated with poor survival (p less than 0.05). The median length of survival of patients with tumors that did not express epidermal growth factor receptor was 40 months compared with 26 months in patients with tumors that did express epidermal growth factor receptor. As in breast and bladder cancer, expression of epidermal growth factor receptor in ovarian cancer appears to be a poor prognostic factor.

Antibodies, Monoclonal↗
PubMed1993

The effect of antibodies and immunotoxins reactive with HER-2/neu on growth of ovarian and breast cancer cell lines.

OBJECTIVE: Because HER-2/neu is overexpressed in one third of breast and ovarian cancers, we examined the effect of unconjugated monoclonal antibodies (ID-5, PB-3, TA-1) and an immunotoxin (TA-1-ricin) reactive with this protooncogene on the growth of breast and ovarian cancer cell lines. STUDY DESIGN: The tritiated thymidine incorporation assay was used to examine the effect of unconjugated antibodies on proliferation. A limiting dilution clonogenic assay was used to assess the effect of immunotoxin on cellular cytotoxicity. RESULTS: Scatchard analysis revealed that OVCA 420, OVCA 429, OVCA 432, and OVCA 433 cells had approximately 10(4) HER-2/neu receptors per cell, whereas the SKOv3 and SKBr3 cell lines expressed 10(5) and 10(6) receptors per cell, respectively. Monoclonal antibody ID-5 caused significant inhibition of tritiated thymidine incorporation in SKBr3, SKOv3, and OVCA 420 cells (p < 0.002). The TA-1-rich immunotoxin significantly inhibited the clonogenic growth of only SKBr3 and SKOv3 cells. CONCLUSION: HER-2/neu may be a useful target for immunotherapy with unconjugated antibodies and immunotoxins in ovarian and breast cancers that overexpress this protooncogene.

Antibodies, Monoclonal↗
PubMed1984

Elevation of serum CA125 in carcinomas of the fallopian tube, endometrium, and endocervix.

An immunoradiometric assay with the use of a monoclonal antibody can detect an antigenic determinant (CA125) in peripheral blood from more than 80% of patients with epithelial ovarian cancer. In this report elevated levels of CA125 were detected in serum from patients with adenocarcinomas of the fallopian tube, endometrium, and endocervix. Among patients with endometrial cancer, CA125 levels were elevated in recurrent or disseminated disease but not with tumors confined to the uterus.

Adenocarcinoma↗
PubMed1985

A study of the NB/7OK and CA 125 monoclonal antibody radioimmunoassays for measuring serum antigen levels in ovarian cancer patients.

Serum levels of tumor antigens NB/7OK and CA 125 were determined in 101 samples by radioimmunoassays with the use of murine monoclonal antibodies. Among serum samples from ovarian cancer patients, elevated NB/7OK levels were found in 87% of samples that contained elevated CA 125 levels. With either assay, only 2% of patients with nonmalignant diseases had elevated antigen levels. No quantitative correlation was found, however, between levels of NB/7OK and CA 125. When antigen present in serum was purified by gel filtration on Sephacryl S-200, CA 125 eluted with an apparent molecular weight in excess of 100 kilodaltons whereas NB/7OK eluted with an apparent molecular weight of 70 kilodaltons. Thus the NB/7OK and CA 125 radioimmunoassays appear to measure two different populations of antigenic material.

Antibodies, Monoclonal↗
PubMed1988

Preoperative evaluation of serum CA 125 levels in premenopausal and postmenopausal patients with pelvic masses: discrimination of benign from malignant disease.

CA 125 levels were measured in 158 patients with palpable pelvic masses who were about to undergo diagnostic laparotomy. When the 68 patients found to have cancer were compared with the 90 patients with benign disease, those with malignancies were significantly older, were more frequently postmenopausal, and had significantly higher values of serum CA 125. Patients with benign pelvic masses had CA 125 levels greater than 65 U/ml in 8% of cases, whereas those with malignancies had CA 125 levels greater than 65 U/ml in 75% of cases. If only those patients who had frankly malignant, primary, nonmucinous epithelial ovarian carcinomas were considered, CA 125 levels greater than 65 U/ml predicted malignancy with a sensitivity of 91% for all patients. Greater sensitivity and specificity were observed in the postmenopausal subgroup than in the premenopausal subgroup. In the postmenopausal group with a 63% prevalence of ovarian cancer the predictive positive value was 98% and the predictive value negative was 72%. In a premenopausal population with a 15% prevalence of ovarian cancer the predictive value for a positive test was 49%, while the predictive value for a negative test was 93%.

Adolescent↗