Home About us Contact
|
Home About us Contact | ||
|
|
||
Repeated Doses (repeated + dose)
Selected AbstractsEffect of Repeated Doses of Ethanol on Hepatic Mg2+ Homeostasis and MobilizationALCOHOLISM, Issue 7 2007Andrew Young The acute administration of a first dose of ethanol (EtOH) to rat liver cells reduces the amount of Mg2+ extruded by a second dose of EtOH or the subsequent addition of adrenergic agonists. In contrast, the Mg2+ extrusion normally elicited by the ,1 -adrenergic or , -adrenergic agonist does not impair the Mg2+ mobilization induced by the subsequent addition of EtOH. Inhibition of EtOH metabolism by 4-methylpyrazole abolishes almost completely the Mg2+ extrusion induced by the first dose of EtOH, and partially enlarges that elicited by the second dose of alcohol or the subsequent adrenergic stimulation. Ethanol-treated liver cells stimulated by the adrenergic agonist show a reduced level of membrane-bound G,s as well as a reduced cellular cAMP content. Analysis of cellular Mg2+ distribution indicates that EtOH administration decreases the Mg2+ content of the cytoplasm, mitochondria, and endoplasmic reticulum to a comparable extent. These data indicate that acute EtOH administration directly impairs cellular Mg2+ homeostasis and also prevents a further Mg2+ mobilization by additional doses of alcohol or ,1 -adrenoceptor and , -adrenoceptor agonist by decreasing cytosolic and intraorganelle Mg2+ content and by affecting G-protein membrane distribution/signaling. [source] Inhibition of microsomal triglyceride transfer protein: Another mechanism for drug-induced steatosis in miceHEPATOLOGY, Issue 1 2003Philippe Lettéron Although many steatogenic drugs inhibit mitochondrial fatty acid ,-oxidation, limited information is available on possible effects on hepatic lipoprotein secretion. In the endoplasmic reticulum (ER) lumen, microsomal triglyceride transfer protein (MTP) lipidates apolipoprotein B (Apo B), to form triglyceride (TG)-rich very low density lipoprotein (VLDL) particles, which follow vesicular flow to the plasma membrane to be secreted, whereas incompletely lipidated Apo B particles are partly degraded. We studied hepatic MTP activity, the lipoproteins present in the ER lumen, and hepatic lipoprotein secretion 4 hours after administration of a single dose of amineptine (1 mmol/kg), amiodarone (1 mmol/kg), doxycycline (0.25 mmol/kg), tetracycline (0.25 mmol/kg), tianeptine (0.5 mmol/kg), or pirprofen (2 mmol/kg) in mice. These various doses have been shown previously to markedly inhibit fatty acid oxidation after a single dose, and to trigger steatosis either after repeated doses (doxycycline) or a single dose (other compounds) in mice. In the present study, amineptine, amiodarone, pirprofen, tetracycline, and tianeptine, but not doxycycline, inhibited MTP activity in vitro, decreased ex vivo MTP activity in the hepatic homogenate of treated mice, decreased TG in the luminal VLDL fraction of hepatic microsomes of treated mice, and decreased in vivo hepatic lipoprotein secretion (TG and Apo B). In conclusion, several steatogenic drugs inhibit not only mitochondrial ,-oxidation, as previously shown, but also MTP activity, Apo B lipidation into TG-rich VLDL particles, and hepatic lipoprotein secretion. Drugs with these dual effects may be more steatogenic than drugs acting only on ,-oxidation or only MTP. [source] Regional anaesthesia for a Caesarean section in women with cardiac disease: a prospective studyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2010E. LANGESÆTER Background We conducted a prospective observational survey of pregnant women with cardiac disease. The aim was to analyse and present the mode of delivery, outcome, and haemodynamic changes during a caesarean section under regional anaesthesia in women with cardiac disease. Methods All pregnant women with a cardiovascular diagnosis, except hypertension, were included in the registry. Based on the cardiac diagnoses, and on the New York Heart Association classification, a multidisciplinary group made recommendations for each patient and decided on the mode of delivery. The data from continuous, invasive haemodynamic monitoring in intermediate- and high-risk patients under regional anaesthesia for a caesarean section were analysed and presented. Results The hospital had approximately 9000 deliveries in the period from November 2003 to April 2008. A total of 113 pregnancies in 107 women were included. Thirty-two (28.3%) pregnancies were classified into the high-risk category. Of 103 deliveries, caesarean sections were performed in 59 (52.2%) cases, with regional anaesthesia in 51 patients (18 emergencies), general anaesthesia in eight patients (five emergencies), and a planned vaginal delivery in 44 patients. There was no mortality among the mothers or the babies during the hospital stay or 6 months postpartum. Pre-operative cardiovascular stability during the caesarean section was maintained by volume and phenylephrine infusion guided by invasive monitoring of haemodynamic variables. Conclusion Our study suggests that pregnant women with cardiac disease may safely deliver the baby by a caesarean section under regional anaesthesia. According to our findings, haemodynamic stability can be obtained by titrated regional anaesthesia, intravenous (i.v.) volume, phenylephrine infusion, and small repeated doses of i.v. oxytocin guided by invasive monitoring. [source] Effect of Cadmium and Aluminum Intake on the Antioxidant Status and Lipid Peroxidation in Rat TissuesJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2001Shohda A. El-Maraghy Abstract This work aimed to study the relationship between the accumulation of cadmium (Cd) or aluminum (Al) in certain tissues and the levels of lipid peroxides as well as tissue antioxidants. To carry out such investigations, CdCl2 was given to rats in two dose levels; 0.5 or 2.0 mg/kg i.p for 1 day or daily repeated doses for 2 weeks. Al was given as AlCl3 either in a single dose of 100 mg/kg or daily repeated doses of 20 mg/kg for 2 and 4 weeks. The measured parameters were tissue malondialdehyde (MDA, index of lipid peroxidation) and reduced glutathione (GSH) levels as well as the activities of glutathione peroxidase (GSH-PX), glutathione reductase (GSSG-R), and glucose-6-phosphate dehydrogenase (G-6-PDH) enzymes. Liver and kidney functions were assessed by measuring serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities as well as serum urea and creatinine concentrations. Cd and Al concentrations in the studied tissues were also measured. Results indicated that tissue Cd was significantly increased after administration of either Cd doses. After a single dose of 0.5 or 2.0 mg/kg CdCl2, the increase in tissue Cd levels were accompanied by an increase in MDA and a decrease in GSH levels. On the other hand, after repeated administration of Cd, tissue Cd accumulation was accompanied by increased hepatic and renal GSH levels with decrease in MDA content and a decrease in GSH-PX activity in liver. Liver function was affected at all dose regimens, whereas kidney function was affected only after 2 weeks administration of the higher dose. In Al treated rats, Al concentration was shown to be increased in liver much more than in brain. This was accompanied by a slight decrease in hepatic GSH level after 2 weeks and a decrease in GSH-PX activity after 4 weeks. Liver function was affected only after repeated injection of Al for 2 or 4 weeks. In general, Al administration exhibited safer pattern than Cd. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:207,214, 2001 [source] Decrease in Langerhans Cells and Increase in Lymph Node Dendritic Cells Following Chronic Exposure of Mice to Suberythemal Doses of Solar Simulated RadiationPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2005Pauline McLoone ABSTRACT Exposure of certain strains of mice to ultraviolet radiation (UVR) causes suppression of some innate and adaptive immune responses. One such consequence of acute UVB exposure is a reduction in the number of Langerhans cells (LC) in the epidermis and an increase in dendritic cells (DC) in lymph nodes draining the irradiated skin sites. Exposure to chronic UVB irradiation also has effects on the immune system, but it is unknown what effects are caused by repeated doses of solar simulated radiation (SSR). Consequently, the main aims of the present study were to determine whether repeated exposure to low doses of SSR would lead to similar changes in these cell populations and whether chronic doses of SSR activate a protective photoadaptation mechanism. Groups of C3H/HeN mice were irradiated daily with 3.7 J/cm2 SSR from Cleo Natural lamps for 2, 10, 20, 30 or 60 days. Further groups of mice received an additional dose of 7.4 J/cm2 SSR on days 2, 10, 30 or 60 to test for photoadaptation. The numbers of LC in the epidermis and DC in the lymph nodes draining irradiated skin sites were counted 24 h after the final irradiation. With the exception of mice irradiated for only 2 days, LC were significantly reduced throughout the chronic irradiation protocol, and no recovery occurred. DC numbers were significantly increased in the draining lymph nodes of mice irradiated for 20 days and 60 days. [source] Intracervical application of the nitric oxide donor isosorbide dinitrate for induction of cervical ripening: a randomised controlled trial to determine clinical efficacy and safety prior to first trimester surgical evacuation of retained products of conceptionBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2005Gabriel Arteaga-Troncoso Objective To determine the therapeutic efficacy and safety of a nitric oxide (NO) isosorbide dinitrate donor to induce cervical ripening of women with missed abortions before surgical evacuation of the uterus. Design A prospective, randomised, double-blind controlled trial. Setting Tertiary referral maternity teaching hospital. Population Sixty women with missed abortions and no cervical dilation. Methods Women requesting surgical evacuation of the uterus were randomly selected to receive endocervical 80 mg/1.5 mL isosorbide dinitrate gel solution (n= 30) or 400 ,g/1.5 mL misoprostol gel solution (n= 30) every 3 hours to a maximum of four doses or until reaching cervical ripening. Vital signs and symptoms were recorded at baseline and then every 3 hours until finishing therapy. Adverse events, such as headache, abdominal pain, pelvic pain, backache, nausea and vomiting, were evaluated. Main outcome measures Probability of reaching cervical ripening >8 mm Hegar dilator; evaluated at 3, 6, 9 and 12 hours after application of isosorbide dinitrate or misoprostol. Results The probabilities of induction of cervical ripening by isosorbide dinitrate and misoprostol after four repeated doses at 3-hour intervals were significantly different (P < 0.001). Efficacy of therapy after 12 hours was 97% for the isosorbide dinitrate group and 70% for the misoprostol group. Systolic and diastolic blood pressures were lower after administration of isosorbide dinitrate than prostaglandin analogues. The difference in the mean systolic and diastolic blood pressure between treatment groups was greatest at 3 hours, with a difference of 7.7 mmHg (P < 0.001) and 5.9 mmHg (P < 0.003), respectively. The most frequent side effect associated with isosorbide dinitrate administration was headache, which occurred in 18 out of 30 patients, compared with only 5 out of 30 women in the misoprostol group [relative risk (RR) 2.41, 95% confidence interval (CI) 1.45,4.03, P < 0.001). Women treated with misoprostol reported mainly pelvic pain (RR 3.24, 95% CI 1.99,5.27, P < 0.001). Conclusions Intracervical administration of 80 mg isosorbide dinitrate in women with missed abortions appears to be effective for cervical ripening prior to surgical evacuation of the uterus. Differences in the incidence of non-serious adverse events are not likely to be clinically significant. [source] A multiinstitutional, concurrent chemoradiation trial of strontium-89, estramustine, and vinblastine for hormone refractory prostate carcinoma involving boneCANCER, Issue 6 2002Wallace Akerley M.D. Abstract BACKGROUND Estramustine phosphate (EMP) and vinblastine have radiosensitizing properties and significant activity against hormone refractory prostate carcinoma. Strontium-89 is a palliative agent that acts as a selective radiation source for bone metastasis. The combination of EMP, vinblastine, and strontium-89 was developed to exploit the potential for radiosynergy. PATIENTS AND METHODS Forty-four patients at the Brown Oncology Group affiliated hospitals were treated with oral EMP 600 mg/m2 daily on Weeks 1,4 and 7,10, vinblastine 4 mg/m2 intravenously once each week on Weeks 1,4 and 7,10, and strontium-89 2.2 MBq/kg on Day 1. Courses were repeated every 12 weeks. Response assessment was based on a change in the serum prostate specific antigen (PSA) levels, correlated with change in measurable disease and bone scan appearance. RESULTS A greater than or equal to 50% decline in PSA for at least 6 weeks was observed in 21 patients (48%, 95% confidence interval, 33,62%). Median duration of response was 23 weeks (range, 6,70.8 weeks). The median survival was 13 months with 1- and 2-year survival rates of 55% and 25%, respectively. After completion of protocol therapy, a retrospective review showed that only nine patients received subsequent palliative external beam radiation after progression. CONCLUSIONS The addition of strontium-89 to the regimen of EMP and vinblastine can be delivered safely and in repeated doses, provides effective palliation, and may decrease the need for future radiation therapy. A randomized trial is necessary to quantify these effects. Cancer 2002;94:1654,60. © 2002 American Cancer Society. DOI 10.1002/cncr.10437 [source] Antenatal corticosteroid therapy: benefits and risksACTA PAEDIATRICA, Issue 2004O Baud Antenatal glucocorticoid therapy remains one the most striking successes in perinatal management of complicated pregnancies leading to premature birth. All women at risk of preterm delivery before 34 weeks gestation should be treated, given the anti-inflammatory and maturative properties of fluorocorticoids. Betamethasone is preferred to dexamethasone and no more than two courses, two weeks apart, should be given, until the evidence from further controlled trials on repeated doses becomes available. [source] | ||||||||||