Effect of a low-protein diet on doxorubicin pharmacokinetics in the rabbit

Summary Malnutrition involving protein deficiency, which commonly occurs in cancer patients receiving anthracycline treatment, is considered to be a risk factor for the development of cardiotoxicity. Protein deficiency has been shown to impair the metabolism of drugs such as theophylline and acetaminophen. If protein deficiency also impairs anthracycline metabolism, it could explain at least in part the enchanced anthracycline toxicity associated with malnutrition. We tested this idea by determining the effect of a low- protein, isocaloric diet on doxorubicin pharmacokinetics in rabbits. The animals were randomized into two groups for 8–12 weeks. Rabbits in group 1 received a low-protein (5%), isocaloric diet, whereas those in group 2 received a normal-protein (15%) diet. Both groups (group 1,n=15; group 2,n=14) were given 5 mg/kg doxorubicin by i.v. bolus. After doxorubicin injection, blood samples were obtained over the next 52 h for the measurement of doxorubicin and doxorubicinol plasma concentrations by high-performance liquid chromatography (HPLC) with fluorometric detection. The low-protein diet significantly decreased doxorubicin clearance (48±3 vs 59±4 ml min^–1 kg^–1;P<0.05), prolonged the terminal climination half-life (28±2 vs 22±2 h;P<0.05), and increased the area under the plasma concentration/time curve extrapolated to infinity (1722±122 vs 1405±71 ng h ml^–1;P<0.05) as compared with the values determined for rabbits fed the standard rabbit chow (15% protein). The volume of distribution for doxorubicin was not altered by the low-protein diet. In addition, in rabbits fed the the low-portein diet, the terminal elimination half-life of the alcohol metabolite, doxorubicinol was prolonged (52±5 vs 40±2 h;P<0.05). Thus, a low-protein diet causes a reduction in the ability of rabbits to eliminate doxorubicin and possibly its alcohol metabolite doxorubicinol. If a similar alteration in anthracycline pharmacokinetics occurs in malnourished cancer patients, this phenomenon may contribute to their increased risk of developing cardiotoxicity associated with anthracycline therapy.Supported by the Department of Veterans Affairs and the American Heart Foundation     

Balloon Catheter with Extra-amniotic Saline Instillation: a Method of Induction in Pregnancies at 41 or More Gestational Weeks

Summary: One hundred five women with a documented pregnancy of 41 weeks' gestation or more, admitted for induction of labour by balloon catheter with extra-amniotic saline instillation, were retrospectively compared to 196 women admitted in spontaneous labour at the same gestational age, with regard to mode of delivery. The success rate of the induction group was 97.1%. The mode of delivery did not differ significantly between the 2 groups. The Caesarean section rates were 11.4% in the induction group versus 9.7% in the spontaneous group. The mode of delivery after induction of labour by balloon catheter with extra-amniotic saline instillation and simultaneously commenced intravenous oxytocin infusion, in pregnancies of 41 weeks or more, is similar to that of spontaneous deliveries at the same gestational age.     

Study on the Relationship between Cytogenetics and Phenotypic Effect in Turner＇s Syndrome

ＳｔｕｄｙｏｎｔｈｅＲｅｌａｔｉｏｎｓｈｉｐｂｅｔｗｅｅｎＣｙｔｏｇｅｎｅｔｉｃｓａｎｄＰｈｅｎｏｔｙｐｉｃＥｆｆｅｃｔｉｎＴｕｒｎｅｒ＇ｓＳｙｎｄｒｏｍｅＨＵＸｉａｏｆｅｎｇ（胡晓峰）；ＺＨＵＢａｏｓｈｅｎｇ（朱宝生）；ＬＩＮＨａｎｈｕａ（林汉华）...     

Effects of Phentolamine on Hemorrheology and Hemodynamics in Dogs with Acute Liver Damage

ＥｆｆｅｃｔｓｏｆＰｈｅｎｔｏｌａｍｉｎｅｏｎＨｅｍｏｒｒｈｅｏｌｏｇｙａｎｄＨｅｍｏｄｙｎａｍｉｃｓｉｎＤｏｇｓｗｉｔｈＡｃｕｔｅＬｉｖｅｒＤａｍａｇｅＤＡＮＺｉｌｉ（但自力）；ＺＨＡＮＧＷｅｎｙｉｎｇ（张文英）；ＬＩＳｈａｏｂａｉ（李绍白）（Ｉｎ...     

Fatty acid profiles in response to soybean oil lipid emulsion infusions in essential fatty acid-deficient miniature swine

The ability of soybean oil lipid emulsions to affect essential fatty acid deficiency (EFAD) and plasma fatty acid distribution was studied in neonatal pigs. The test animals were maintained on a fat-free diet prior to administration of lipid emulsion. Plasma and red blood cell (RBC) membrane levels of essential [linoleic (C-18:2 omega 6) and arachidonic (C-20:4 omega 6)] and nonessential [palmitic (C-16, palmitoleic (C-16:1 omega 7), stearic (C-18), and oleic (C-18:1 omega 9)] fatty acids and the triene:tetraene ratio [5,8,11-eicosatrienoic acid (C-20:3 omega 9):arachidonic acid (C-20:4 omega 6)] were monitored to ascertain the establishment of EFAD and its correction. Nonessential fatty acids were studied, as these components of lipid therapy have received little attention. Results indicate that soybean oil emulsions are effective in reversing fatty acid profiles found in EFAD, and both essential and nonessential fatty acids are under strict metabolic control.