Estrogen absorption and metabolism in postmenopausal women with end-stage renal disease

Women with end-stage renal disease (ESRD) have a higher rate of death from heart disease than women with normal renal function. Because estrogen replacement therapy may significantly decrease the incidence of death due to cardiovascular disease in postmenopausal women with normal renal function, their use has been considered for women with ESRD. However, the pharmacokinetics of estrogen have not been studied in postmenopausal women with ESRD to determine the optimal estrogen dose. Six postmenopausal women with ESRD receiving maintenance hemodialysis and six controls matched for body mass index were admitted to the in-patient Clinical Research Center. A 1- or 2-mg oral estradiol (E2) pill was given while subjects fasted. Blood sampling was performed over the next 24 h for measurement of E2, estrone (E1), albumin, and sex hormone-binding globulin (SHBG). Three weeks later, the subjects were given the other E2 dose under identical conditions. At baseline, total and free E2 levels were higher in the subjects with ESRD than in controls (P = 0.0005 and 0.0035, respectively). After ingestion of 1 and 2 mg E2, total and free E2 levels remained significantly higher in the ESRD subjects from 2-8 h after treatment (P < or = 0.05). After 1 mg oral E2, total serum E2 peaked at 65 pg/mL at 4 h in ESRD subjects and at 27 pg/mL in control subjects at 8 h. After 2 mg oral E2 treatment, total serum E2 peaked at 8 h in both ESRD and control subjects, with levels of 99 and 37 pg/mL, respectively. E1 was higher in the subjects with ESRD than in the control subjects at baseline (P < 0.05). After ingestion of 1 mg E2, E1 concentrations were not significantly higher in ESRD than in control subjects, peaking at 180 and 121 pg/mL, respectively (P = 0.3). E1 concentrations were higher in ESRD than in control subjects after the ingestion of 2 mg E2, with peak levels of 376 and 201 pg/mL, respectively (P = 0.03). Total and free E2 levels are higher in patients with ESRD than in control subjects at baseline and after E2 ingestion, indicating that renal failure alters the pharmacokinetics of both endogenous and exogenous E2. Therefore, conventional E2 doses used in individuals with normal renal function may be excessive for patients with ESRD.     

Midtrimester pregnancy termination for fetal malformations. Use of intravaginal prostaglandin E2

OBJECTIVE: To compare outcome differences and responses to treatment in pregnancies complicated by either major fetal malformations or previous fetal death in the second trimester. STUDY DESIGN: Data were analyzed from a computerized perinatal database and individual hospital records for singleton gestations between 14 and 23 weeks undergoing labor induction with prostaglandin E2 (PGE2) suppositories (20 mg intravaginally every three to five hours). RESULTS: Between January 1993 and June 1995, 65 pregnancies underwent induction of labor for either a lethal fetal malformation (38) or death (27). As compared with the fetal death group, the malformation group required more suppositories (median 4, range 1-10, versus median 3, range 1-6; P < .05) and needed a greater total dosage (77.5 +/- 38.5 mg versus 61.8 +/- 37.8 mg, P < .05). The mean time from initiation of treatment until delivery was two hours longer in the malformation group. There were no significant differences between the two treatment groups in incidence of maternal side effects or of retained placentas requiring operative intervention. CONCLUSION: Patients who undergo second-trimester induction of labor for major fetal malformations using intravaginal PGE2 should be counseled that the dosage of the drug is greater and that labor may last longer than in pregnancies complicated by a previous fetal death.     

Development of an HSV-based vector for the treatment of Parkinson's disease

The restricted pattern of neurodegeneration seen in Parkinson's disease, and the identification of trophic factors that prevent toxin-induced degeneration of dopaminergic neurons, has spurred research into potential gene therapy for this disease. Herpes simplex virus (HSV-1) is a neurotrophic virus which naturally establishes latency in neurons. HSV-based vectors have been demonstrated to transfer and transiently express transgenes in neurons in brain in vivo. Recent experiment have shown that deletion of multiple immediate-early HSV genes reduces the potential cytotoxicity of these vectors, and in addition results in altered patterns of transgene expression that may allow for long-term expression required for human gene therapy applications.     

Effects of a dietary mixture of meat and bone meal, feather meal, blood meal, and fish meal on nitrogen utilization in finishing Holstein steers

Our objective was to determine to what extent rate and efficiency of protein gain in finishing cattle can be enhanced by feeding an amino acid-balanced mixture of undegraded intake proteins. The Cornell Net Carbohydrate and Protein System (CNCPS) model was used to formulate a corn-based diet that would meet the rumen requirements for 410-kg large-framed steers with an estrogen implant and fed an ionophore. The CNCPS model was also used to formulate a highly undegradable intake protein (UIP) mixture from meat and bone meal, blood meal, fish meal, and hydrolyzed feather meal to provide the amino acids needed to supplement those derived from microbial protein to better meet amino acid requirements for growth. Four Holstein steers weighing 407 kg were offered a 90:10 concentrate-forage diet at hourly intervals at 95% of ad libitum intake. The steers were injected with 500 microg of estradiol-17beta at 12-h intervals to mimic the effects of an estrogenic implant. Treatments planned consisted of inclusion of the UIP mixture at 0, 2.5, 5, and 7.5% of the diet DM. Dry matter intake was fixed at 6.4 kg/d, and DM digestibility was not significantly affected by varying the amount of UIP addition. Apparent digestibility of N increased (P = .011) from 63.8 to 65.8, 70.7, and 71.5%, the amount of N absorbed increased (P = .001) from 73 to 84, 100, and 106 g/d, and N balance increased (P = .003) from 20 to 30, 33, and 39 g/d when UIP was fed at 0, 2.6, 5.2, and 7.8% of diet DM, respectively. The efficiency of N use increased 39.7%, and biological value increased 31.6% when the UIP mixture was added to the diet. Circulating concentrations of plasma urea N (PUN) were increased (P = .017) from 4.5 for the control diet to 5.7, 6.2, and 6.1 mg/dL when the UIP mixture was added at 2.6, 5.2, and 7.8%, respectively. Corresponding IGF-I concentrations were also increased from 491 to 558 and 624 ng/mL with 2.6 and 5.2% levels of UIP addition. Plasma glucose, NEFA, and insulin concentrations were not affected by feeding the UIP mix. The rate and efficiency of N use for growth improved with addition of an amino acid-balanced UIP mixture to the diet.     

Mitosis in living budding yeast: anaphase A but no metaphase plate

Chromosome movements and spindle dynamics were visualized in living cells of the budding yeast Saccharomyces cerevisiae. Individual chromosomal loci were detected by expression of a protein fusion between green fluorescent protein (GFP) and the Lac repressor, which bound to an array of Lac operator binding sites integrated into the chromosome. Spindle microtubules were detected by expression of a protein fusion between GFP and Tub1, the major alpha tubulin. Spindle elongation and chromosome separation exhibited biphasic kinetics, and centromeres separated before telomeres. Budding yeast did not exhibit a conventional metaphase chromosome alignment but did show anaphase A, movement of the chromosomes to the poles.     

Characterization of recombinant adeno-associated virus-2 as a vehicle for gene delivery and expression into vascular cells

Investigations into the incidence of Salmonella abortus ovis (S. abortus ovis) infections should not be neglected in diagnosis of ovine abortion cases. For detection of this pathogen agent, direct cultivation, as well as pre-enrichment combined with enrichment procedures in tetrathionate or Rappaport-Vassiliadis medium, should be performed with respect to the features of S. abortus ovis. The detection limit of S. abortus ovis using pre-enrichment and enrichment media could be determined using 6.5 x 10(3)-6.5 x 10(4) bacteria. For subsequent cultivation of S. abortus ovis Gassner, XLD or Rambach agar are suitable. In infected sheep showing no excretion of S. abortus ovis, the pathogen can be detected by serological studies using microagglutination or the ELISA test. The ELISA test proved to be more sensitive than the microagglutination test, detecting antibodies against S. abortus ovis in 17% of the 814 sheep tested. The microagglutination test revealed positive results in only 2% of the sheep tested.