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Biomedical subjects

R R Evans

Publications and source records attributed to R R Evans.

At least 19 recordsLinked to original sources

Birth of a western lowland gorilla (Gorilla gorilla gorilla) following in vitro fertilization and embryo transfer.

A 21-year-old multiparous female exhibiting 31-41 day menstrual cycles was given hFSH (225 IU/day, Metrodin 75, from cycle day 3 through 9 (menses = day 1) and hCG (10,000 IU, Profasi, on day 10 to stimulate follicular development. At 35 h after hCG, under isoflurane (AErrane) anesthesia, follicles were aspirated by controlled suction under transvaginal ultrasound guidance. Metaphase II oocytes (n = 11) were placed in modified human tubal fluid (mHTF, 100 microliters) medium under oil at 37 degrees C in humidified 5% CO2. Frozen semen, collected by voluntary ejaculation, was thawed (70 degrees C H2O bath, 6 sec), diluted slowly, centrifuged, and resuspended in mHTF, and 160,000 motile spermatozoa/ml were added at 6 h after oocyte recovery. At 21 h postinsemination (p.i.) eight oocytes were at the two-cell stage, five were cryopreserved, and three were cultured to the six- to eight-cell stage in mHTF with granulosa cells before transcervical uterine transfer at 47 h p.i. using a Teflon catheter. Micronized progesterone (400 mg/d) was orally administered for 10 weeks posttransfer (p.t.). Ultrasound examination revealed a single fetus at 15 weeks p.t., and unassisted delivery of a live 1.37 kg female infant occurred at 29 weeks. Am. J. Primatol. 41:247-260, 1997.

Animals

Norgestomet implants prevent pregnancy in beef heifers on pasture.

The efficacy of erodible norgestomet implants for preventing pregnancy in postpubertal heifers was evaluated in two experiments at five locations each. Heifers (n = 896) within each study location were stratified by weight and allotted randomly to receive an ear implant containing either 0, 24, 36, or 48 mg of norgestomet (d 0). Heifers were exposed to fertile bulls immediately after implantation for 75 d (d 0 to 74) in Exp. 1 (n = 476) or for 80 d (d 75 to 154) in Exp. 2 (n = 420). Weights were recorded on d 0 and 74 (Exp. 1 and 2) and d 154 (Exp. 2). Each heifer was palpated rectally for pregnancy at the end of each experiment. Pregnancy rates were higher (P < .01) for control heifers (0 mg implant) than for heifers that received 24, 36, or 48 mg of norgestomet. In Exp. 1, pregnancy rates were 96, 29, 6, and 4% for heifers that received 0, 24, 36, and 48 mg implants of norgestomet, respectively. In Exp. 2, pregnancy rates were 85, 36, 19, and 9% for heifers that received 0, 24, 36, and 48 mg implants of norgestomet, respectively. Estrous activity during the first 3 wk of bull exposure was reduced (P < .05) among heifers that received norgestomet implants compared to control heifers but was not completely abolished at any dosage in Exp. 1. During the first 75 d of Exp. 1 and 2, heifers treated with 36 or 48 mg norgestomet implants gained weight faster (P < .05) than control heifers. Combined across both experiments, ADG during the first 74 d were .53, .56, .59, and .60 kg/d for heifers treated with 0, 24, 36, and 48 mg implants of norgestomet, respectively. These data indicate that norgestomet implants increased rate of weight gain, reduced estrous activity, and reduced the occurrence of pregnancy in heifers on pasture.

Animal Feed

New or developing antihypertensive agents.

Although significant pharmacologic and nonpharmacologic advances in treating hypertension during the last decade have reduced mortality and morbidity, hypertension continues to be a major health concern worldwide. Therefore, the search continues for newer specific pharmacologic treatment of this disorder. This review focuses on pharmacologic agents or classes of agents either recently approved or under clinical development for the treatment of hypertension.

Animals

Seasonal pattern of inhibition of Ostertagia ostertagi in calves in northeast Mississippi.

The composition of, and seasonal changes in, populations of gastrointestinal parasites of calves in northeast Mississippi were determined for 10 months post-weaning. After weaning on 15 October, 20 mixed breed beef steers were grazed together on a 4 ha fescue/bermudagrass pasture. From November through August of the following year, two of the calves were removed each month for necropsy and counting of gastrointestinal nematodes. Eight species of worms were found: Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Bunostomum phlebotomum, Cooperia spp., Trichostrongylus colubriformis, Oesophagostomum spp., and Trichuris ovis. During all months, Ostertagia ostertagi and Cooperia spp. combined comprised at least 89% of gastrointestinal nematode burdens. Cooperia spp. represented 92.6% of the total worm burden of calves in November but declined to about 56% in January and February. From March through August, Ostertagia ostertagi comprised at least 79% of the worms from calves. Numbers of inhibited Ostertagia ostertagi increased markedly from February to March and remained at high levels prior to resumption of development in August. The proportion of Trichostrongylus axei remained about 4% throughout the year, but the highest numbers were recorded in the summer months. Other species were minor components of the worm population. These data indicate that with respect to Ostertagia ostertagi, northeast Mississippi can be considered a summer inhibition zone.

Abomasum

Epidemiological study of nematode infections in a grazing beef cow-calf herd in Mississippi.

The epidemiology of gastrointestinal nematodes was studied in a spring calving herd in northeast Mississippi. Pregnant, mixed breed beef cows (n = 15) were placed on a 10 ha fescue/bermuda grass pasture from January 1990-February 1992. In both years, calves were born from February-April and were weaned and removed from the pasture in mid-October. Fecal egg counts (EPG) and generic composition of nematodes in fecal cultures were determined monthly for cows and calves. Estimation of numbers of third-stage larvae on herbage also was determined monthly from March 1990-February 1992. Worm-free tracer calves (2-3 per month) were allowed to graze for 1 month periods and slaughtered for counting and identification of gastrointestinal nematodes. The mean monthly EPG of cows was consistently low (0.23-3.41); EPG of calves increased from spring through fall of both years. Five nematode genera were identified from fecal cultures of cows and calves. Ostertagia and Trichostrongylus spp. were the predominant nematodes in cows, while Ostertagia and Cooperia spp. were predominant in calves. Numbers of third-stage larvae on herbage declined from spring through summer and remained at low levels until late fall/winter, when numbers increased markedly. Eleven nematode species were identified from tracers, but O. ostertagi and Cooperia spp. predominated in most months. Seasonal changes in tracer worm counts coincided with similar changes in counts of third-stage larvae on herbage. Inhibition of O. ostertagi occurred in tracer calves during spring, but did not give rise to a marked increase in egg production in cows during fall.

Animals

Racial and gender differences in endothelin-1.

In summary, ET-1 levels were significantly increased in black men compared with white men. This racial difference could have important research implications if increased ET-1 levels are linked to left ventricular hypertrophy and other cardiovascular diseases, and it may serve as a foundation for future studies.

Adolescent

Gene therapy and endothelial cell targeting for cancer.

The endothelium represents a potentially critical target for gene therapy because of its anatomical location and its importance in the viability in both normal and malignant tissues. Protecting the endothelium of normal tissues, such as the lungs, from the toxic effects of current antineoplastic agents and the destruction of the tumor vasculature are reasonable goals. As a target, however, the endothelium continues to represent a significant challenge. While gene delivery to cultured endothelial cells is possible, improved delivery systems are required, as well as cell-specific promoters, before in vivo gene therapy to important endothelial populations can be accomplished.

Amino Acid Sequence

Saturable elimination and saturable protein binding account for flavone acetic acid pharmacokinetics.

Flavone acetic acid (FAA) is an antineoplastic agent that has undergone extensive study in Phase I trials. Concentration-dependent plasma protein binding has been demonstrated in vitro at concentrations of total drug that are achieved in vivo. Moreover, dose-dependent total systemic clearance has been described when FAA has been administered as a short iv infusion. When administered as a prolonged 24-hr infusion, total FAA (bound plus unbound) plasma pharmacokinetics are well described with a first-order two-compartment model. However, measurement of unbound FAA intra- and post-intravenous infusion in eight patients revealed a twofold increase in fraction of FAA unbound in plasma intrainfusion. We attempted to fit pharmacokinetic structural models of varying complexity to the unbound concentrations alone and simultaneously to the unbound and bound FAA plasma concentrations. The data were adequately described only by a model that incorporated simultaneous saturable plasma protein binding and a Michaelis-Menten process for elimination. A comparison among models is presented, as well as pharmacokinetic parameter estimates for FAA in children. These clinical data are consistent with predictions of the clearance model in which both saturable protein binding (resulting in a dynamically increasing unbound fraction) and saturable elimination (resulting in gradually decreasing unbound intrinsic clearance) are operative.

Antineoplastic Agents

Automated high-performance liquid chromatographic assay for the determination of 7-ethoxycoumarin and umbelliferone.

An improved high-performance liquid chromatographic assay is presented for the determination of 7-ethoxycoumarin O-deethylase activity. Following a 30-min microsomal incubation, 7-ethoxycoumarin, 4-methylumbelliferone (internal standard), and the metabolite umbelliferone were extracted with chloroform. Separation was achieved with an isocratic mobile phase using a microBondapak phenyl (300 mm x 3.9 mm I.D.) analytical column. The effluent was monitored by fluorescence detection with an excitation wavelength of 360 nm and an emission wavelength of 470 nm. The intra- and inter-assay coefficients of variation were 10 and 6%, respectively. A detection limit of 0.07 micrograms/ml was achieved, making this method suitable for characterizing P-450 activity of human livers.

7-Alkoxycoumarin O-Dealkylase

Humoral factors determining the blood pressure response to converting enzyme inhibition and calcium channel blockade.

Renin and catecholamine levels were determined in patients with mild to moderate hypertension before and after treatment with sustained release diltiazem or captopril and were correlated with the blood pressure response to these antihypertensives. Eight weeks of treatment with either agent led to equal decreases in both systolic and diastolic blood pressure. Pretreatment plasma renin activity (PRA) and plasma norepinephrine did not predict the blood pressure response to either agent. Diltiazem significantly increased both PRA and supine norepinephrine levels. However, in the diltiazem treated patients, there was no correlation between the change in plasma norepinephrine and the change in systolic or diastolic blood pressure. In contrast, there was a negative correlation (P less than .05) between the reactive rise in PRA and the decrease in systolic blood pressure. Thus, the antihypertensive response to a calcium channel blocker may be determined, in part, by the reactive response of pressor systems.

Adult

Effects of calcium channel blockade on calcium homeostasis in mild to moderate essential hypertension.

Calcium channel blockers may alter parathyroid hormone secretion in vitro, which would alter calcium homeostasis. To determine the chronic effect of calcium channel blockade in vivo, we conducted a randomized, double blind, 16 week study comparing the effects of two pharmacologic antihypertensive agents, the calcium channel blocker diltiazem and the angiotensin-converting enzyme inhibitor captopril on parameters of calcium homeostasis. Both diltiazem and captopril lowered blood pressure to a similar degree. Neither drug produced any significant change in blood levels of total and ionized calcium, magnesium, or phosphorus, which affect the regulation of parathyroid hormone and vitamin D. In addition, at eight or 16 weeks following initiation, neither drug altered the serum levels of parathyroid hormone (PTH) or 1,25-(OH)2-vitamin D3 (1,25-D). Chronic calcium channel blockade with diltiazem does not alter serum parameters of calcium homeostasis and, thus, should not affect bone mineralization.

Adult

Sustained-release diltiazem: duration of antihypertensive effect.

The antihypertensive activity of a sustained-release preparation of diltiazem (given each 12 hours) was assessed in 96 patients with supine diastolic blood pressure (BP) between 95 and 110 mm Hg in a multicenter, randomized, double-blind, placebo run-in, parallel-group trial comparing optimally titrated doses of diltiazem and placebo. The aim was to assess the onset of action as well as the extent and variability of BP control of this formulation during the 12-hour interval. Diltiazem was titrated from 120 mg bid to 180 mg bid as necessary to lower BP. At baseline, on the first day of titration, and at the end of 8 weeks, BP was evaluated at 0, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dosing. The onset of action was within 2 hours, and the effect was maintained throughout the 12-hour period. Mean BP for the diltiazem group at baseline was 154/101 mm Hg. At week 8, BP was 148/93 mm Hg at hour "0" (P less than .02 and P = .0001 for systolic and diastolic BP vs. placebo), 139/84 mm Hg at the nadir at hour 5 (P = .0001), and 149/91 mm Hg at the end of the 12-hour period (P less than .02 and P = .0001 for systolic and diastolic BP). Diltiazem was significantly more effective than placebo (P = .0001) with 50% of patients controlled to a diastolic pressure of less than 90 mm Hg at 7 of the 10 evaluation points, including the evaluation point of 12 hours post-dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Metabolic effects of antihypertensive therapy with a calcium antagonist.

The effect of diuretics to increase serum glucose, low-density lipoprotein cholesterol and triglycerides, as well as the adverse changes in triglycerides and high-density lipoprotein cholesterol produced by nonselective beta blockers, have been largely ignored in the treatment of hypertension. However, a number of trials have shown that reductions in serum lipids can alter cardiovascular mortality. Calcium antagonists have become major drugs in the treatment of hypertension, and some data suggest that calcium antagonists may increase serum glucose levels. Significantly less data on lipid effects have been published. Lipid and glucose effects were examined in an 8-week antihypertensive study using a sustained-release preparation of diltiazem titrated from 240 to 360 mg/day in a twice-daily regimen in a randomized, double-blind, placebo-controlled parallel trial in 96 patients. Average supine blood pressure at week 8 was 156/98 mm Hg, standing blood pressure with placebo 152/100 mm Hg, and with diltiazem 147/91 and 144/93 mm Hg. There were no statistically significant changes in serum lipids or glucose in the diltiazem or placebo group or between the groups. Mean values (mg/dl) at baseline and week 8 in the diltiazem group were, respectively, for cholesterol 215 and 218, high-density lipoprotein cholesterol 50 and 51, low-density lipoprotein cholesterol 128 and 133, triglycerides 169 and 175, and glucose 113 and 110. Thus, this large and placebo-controlled study shows that diltiazem is among the antihypertensives with no adverse long-term lipid or glucose effects.

Blood Glucose

Efficacy of a morantel sustained-release bolus for control of gastrointestinal parasites in winter-grazed steers in Mississippi.

From Nov 22, 1983 through May 15, 1984, 36 crossbred steers were allotted into 3 treatment groups (12/group) and were grazed on separate 3.4-hectare pastures. On Nov 22, 1983, the steers were administered a single morantel sustained-release bolus (MSRB), orally (group 1), or a single dose of thiabendazole (TBZ; 66 mg/kg of body weight, orally; group 2), or were left untreated (group 3; controls). Animal weights, nematode egg counts in fecal specimens, and plasma pepsinogen concentrations were monitored monthly. At the termination of the study, 4 steers from each treatment group were slaughtered and necropsied and worm counts were determined. A set of parasite-free tracer calves (3/treatment group) were grazed with each treatment group for 1 month, beginning on Nov 22, 1983; a second set of tracer calves (3/group) were grazed with each treatment group for 1 month, beginning Apr 3, 1984. At the end of their respective grazing periods, tracer calves were held for 3 weeks and then were slaughtered and necropsied and their worm counts were determined. Mean nematode egg counts in fecal specimens of group 1 (MSRB treated) were significantly lower (P less than 0.05) than that of the TBZ-treated or nontreated steers. Differences in worm counts were not found between treatment groups. Differences in worm counts of tracer calves were not found among the 3 groups for November 1983 nor for April 1984. Steers treated with the MSRB had a higher mean weight gain (P less than 0.06) than did the control or TBZ-treated steers.

Animals

Field efficacy of a morantel sustained release bolus for control of gastrointestinal nematodes in yearling steers.

The efficacy of a morantel sustained release bolus (MSRB) for control of gastrointestinal nematodes in yearling steers was evaluated over a 6-month grazing period commencing on 26 March 1982. Three groups of 15 steers were allotted to the following treatments: Group 1 -- one MSRB at start of trial; Group 2 -- one therapeutic dose of thiabendazole at start of trial; Group 3 -- untreated control. The treatment groups were grazed separately. Parasite egg counts (EPG), herbage larval counts, pepsinogen levels and weight gains were monitored. Every other month, sets of 2 parasite-free tracer calves were placed in the pasture grazed by each treatment group and allowed to graze for 3 weeks before being subsequently necropsied for worm counts. At the end of the trial, 6 animals from each group were also necropsied for worm counts. The MSRB treatment resulted in significantly lower egg counts, fewer infective larvae on pasture, lower pepsinogen levels and lower worm burdens in tracer calves than was the case for the untreated group, but generally the levels were not significantly different from those associated with the thiabendazole treatment. The mean weight gain for the MSRB treated steers showed a significant advantage (70.9 lb) over the untreated animals, but was not significantly different from those which received thiabendazole. Total worm counts at the end of the trial were not different from any treatment group.

Abomasum

Enalaprilat, an intravenous angiotensin-converting enzyme inhibitor, in hypertensive crises.

The effect of enalaprilat (MK-422), a newly synthesized, intravenous, nonsulfhydryl, angiotensin-converting enzyme inhibitor, was studied in seven patients with either severe or malignant hypertension. All subjects initially received a 1 mg bolus injection of enalaprilat followed in 30 minutes by 10 mg. Five subjects received an additional 40 mg. Mean (+/- SE) pretreatment blood pressure for the group was 226 +/- 9/141 +/- 7 mm Hg. Five minutes after the 1 mg enalaprilat dose, blood pressure decreased to 211 +/- 10/131 +/- 9 mm Hg and further fell to 201 +/- 14/123 +/- 11 mm Hg at 30 minutes. The maximal reduction in blood pressure to 169 +/- 14/112 +/- 10 mm Hg occurred 30 minutes after the 10 mg dose. No further blood pressure reduction was observed in those subjects who received the additional 40 mg dose. Within the entire group, five subjects exhibited sustained blood pressure reduction. No adverse side effects or symptomatic hypotension occurred in any subject.

Adult

Properties of smooth muscle vinculin.

Vinculin, isolated from turkey gizzard smooth muscle, was purified by chromatography on CM-cellulose after isolation from a DEAE-cellulose column. Two-dimensional gel electrophoretic analysis of crude muscle fractions demonstrated that: 1) much of the approximately 130,000-dalton protein present in smooth muscle did not co-isoelectrically focus with the purified 130,000-dalton vinculin and 2) the purified vinculin consisted of three major, closely spaced isoelectric variants that were present only in small amounts in the original smooth muscle sample. Purified vinculin sedimented as a single peak with a sedimentation coefficient S0 20,w of 5.9. Circular dichroism spectra of purified vinculin indicated a considerable degree of secondary structure, with an alpha-helical content of approximately 50% as measured at 208 nm. The ultraviolet absorption spectrum of vinculin gave a measured E1%(278) of 4.64. Digestion of vinculin, much of which is located at the cytoplasmic surface of the cell membrane, with Ca2+-activated neutral protease purified from skeletal muscle yielded major fragments with molecular weights determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 98,000, 85,000, and 26,000. The factor(s) in DEAE-cellulose-purified vinculin responsible for decreasing the low shear viscosity of actin was removed and found in a crude fraction isolated by CM-cellulose chromatography. The purified vinculin had a small, but positive effect on the MgCl2-induced polymerization of actin as measured by low shear viscometry.

Amino Acids