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Biomedical subjects

J A Olson

Publications and source records attributed to J A Olson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Vitamin A status of Indonesian children infected with Ascaris lumbricoides after dosing with vitamin A supplements and albendazole.

In developing countries, both marginal vitamin A status and intestinal helminths are common among children. Indonesian children (n = 309, 0.6-6.6 y), known to be infected with Ascaris lumbricoides, were randomized into six different treatment groups (A-F). The treatments included 210 mumol vitamin A supplement and a dose of 400 mg albendazole (5-propylthio-1H-benzimidazol-2-yl carbamic acid methyl ester) administered orally either at the same health visit (Groups B and F) or at different contact times during a 1-mo period (groups A, C, D and E). Vitamin A status was assessed both before and 3-4 wk after the treatments by the modified relative dose response (MRDR) test. Vitamin A supplementation was most important in improving the vitamin A status (P < 0.0001) of these children, whereas treatment for ascariasis alone (P = 0.370) and the statistical interaction between treatment for ascariasis and vitamin A (P = 0.752) were not. Serum retinol concentrations marginally improved (P = 0.051) in two of the groups that received vitamin A and albendazole but not in the third group that received vitamin A only. The MRDR test proved a better discriminator of the effects of these treatments on vitamin A status than changes in serum retinol concentrations.

Albendazole↗
PubMed1996

Benefits and liabilities of vitamin A and carotenoids.

Vitamin A and carotenoids are often cited as members of a family of antioxidant vitamins that can show protective effects against oxidative stress and some chronic diseases. The great advantages of aerobic metabolism are offset in part by adverse physiological effects that can be caused by highly reactive forms of oxygen and its reduction products. Nature has developed a variety of sophisticated defenses against these undesirable side effects of oxygen. Vitamin A and carotenoids can serve chemically both as electron acceptors and donors (i.e., as oxidants and reductants), although in nature vitamin A seems to be protected from oxidation by other physiological antioxidants rather than serving a protective role itself. Furthermore, large doses of vitamin A are toxic. Carotenoids may serve a broader protective role in humans as they do in plants and microorganisms, but the evidence supporting such a role in humans is mixed. The widely used term antioxidant vitamins is too narrow in scope for the properties attributed to them. A much better term is physiological modulators, which broadens both the set of compounds that are included and the possible nature of their actions, whether beneficial or adverse.

Animals↗
PubMed1996

Bioactivities of N-(4-hydroxyphenyl) retinamide and retinoyl beta-glucuronide.

N-(4-Hydroxyphenyl) retinamide (4HPR) and retinoyl beta-glucuronide (RAG) are two derivatives of all-trans retinoic acid (RA) that show properties both similar to as well as different from their parent compound, RA. Both retinoids possess the important property of showing much-reduced toxicity relative to RA while maintaining significant biological activity. 4HPR, a synthetic derivative, is active in the prevention and treatment of a variety of neoplasms in animals, and by inducing apoptosis, shows growth inhibitory activity against many human tumor cell types in vitro. In humans, 4HPR reduces the incidence of new occurrences of leukoplakia and is currently being tested as a preventive agent for breast cancer. RAG, a naturally occurring metabolite of RA, effectively stimulates the growth of vitamin A-deficient animals, induces the differentiation of epithelial cells in vivo and in vitro, and is effective in the topical treatment of acne in humans. Unlike RA, RAG is nontoxic when applied to the skin and is nonteratogenic when given orally to rats. Possible mechanisms of action of both compounds are discussed. These two derivatives of retinoids show interesting physiologic effects and potentially beneficial pharmacologic actions.

Animals↗
PubMed1996

Parathyroid autotransplantation during thyroidectomy. Results of long-term follow-up.

SUMMARY BACKGROUND DATA: Permanent hypoparathyroidism is a recognized complication of thyroidectomy. Operative strategies to prevent this complication include preservation of parathyroid glands in situ and autotransplantation of parathyroid glands resected or devascularized during thyroidectomy. METHODS: An analysis of 194 patients having thyroidectomy and simultaneous parathyroid autotransplantation at Barnes Hospital from 1990 to 1994 was performed. Data were collected regarding patient demographics, indication for thyroidectomy, operative procedure, pathologic diagnoses, and postoperative course, including biochemical assessment of parathyroid autograft function. RESULTS: Of 194 patients having either total, subtotal, or completion thyroidectomy, 104 (54%) experienced a [Ca(+2)]nadir less than or equal to 8.0 mg/dL and had symptoms and signs of hypocalcemia. Parathyroid autotransplantation was successful in 103 (99%) of these 104 cases and resulted in a 1.0% incidence of hypoparathyroidism in this series. CONCLUSIONS: Although preservation of parathyroid glands in situ is desirable, routine parathyroid autotransplantation during thyroidectomy virtually eliminates postoperative hypoparathyroidism. Normal parathyroid glands resected or devascularized during thyroidectomy for well-differentiated thyroid carcinoma or benign disease should be transplanted in the sternocleidomastoid muscle. Patients with Multiple Endocrine Neoplasia type 2A should have parathyroid glands resected at the time of thyroidectomy for medullary thyroid carcinoma and transplanted in the nondominant forearm. Postoperative management in most patients after thyroidectomy and parathyroid autotransplantation involves temporary calcium and vitamin D replacement and close biochemical evaluation. This precautionary measure of parathyroid autotransplantation markedly reduces the incidence of permanent postoperative hypoparathyroidism.

Adolescent↗
PubMed1996

Percutaneous absorption, excretion and metabolism of all-trans-retinoyl beta-glucuronide and of all-trans-retinoic acid in the rat.

The purpose of these studies was to compare directly the percutaneous absorption,excretion and metabolism of all-trans-retinoyl beta-glucuronide (RAG), a nontoxic retinoid, with all-trans-retinoic acid (RA) in the rat. Previously, it was demonstrated that topical treatment of human acne with either RAG or RA in cream resulted in a significant reduction of lesions. Whereas 0.1% RA showed adverse effects, concentrations of RAG up to 2.4% did not cause any adverse reactions. In the present studies, radiolabeled RAG or RA, dispersed in a water-based cream, was applied to the shaved dorsal skin of vitamin A-sufficient rats. Both RAG and RA were absorbed from the skin in a similar way. In both cases, radioactivity peaked in the plasma within 2-4 h and within the liver at 4-12 h. During a 7-day period, the overall excretion of radioactivity derived from RA and RAG in the feces and urine were similar, e.g. 17 and 12%, respectively. it is concluded that: (1) the transport, metabolism and excretion of topically applied radioactive RA and RAG are similar, although not identical, in the rat and (2) the toxic skin manifestations induced by RA but not by RAG cannot be attributed to major differences in their overall absorption, metabolism and excretion.

Administration, Topical↗
PubMed1995

Intestinal absorption, serum clearance, and interactions between lutein and beta-carotene when administered to human adults in separate or combined oral doses.

Single equimolar doses (0.5 mumol/kg body wt) of lutein and/or beta-carotene in true solution in oil were given to eight adult subjects and 13 blood samples were taken during the subsequent 840 h. Whereas the mean serum concentration of lutein showed a single maximum at 16 h, that of beta-carotene peaked at 6 h and then again at 32 h. Subsequently, lutein and beta-carotene were cleared at approximately the same rate from the serum. The mean (+/- SEM) areas under the curve (AUCs) for lutein and beta-carotene during the first 440 h differed significantly: 59.6 +/- 9.0 and 26.3 +/- 6.4 mumol.h/L, respectively (P < 0.005). AUC values did not correlate with initial serum concentrations of the given carotenoid or with the order of dosing. When combined in the same dose, beta-carotene significantly reduced the serum AUC values for lutein to 54-61% of control values (P < 0.025), whereas lutein reduced the AUC value for beta-carotene in five subjects but enhanced it in three subjects. Effects of lutein on the AUC for beta-carotene were inversely related to the AUC for beta-carotene alone. Thus, carotenoids clearly interact with each other during intestinal absorption, metabolism, and serum clearance, although individual responses can differ markedly.

Administration, Oral↗
PubMed1995

Pharmacokinetics, oral bioavailability and tissue distribution of azithromycin in cats.

Azithromycin is the first of a class of antibiotics classified as azalides. In an initial experiment four cats were given a single dose of azithromycin 5 mg/kg orally (p.o.), followed 2 weeks later by a single intravenous bolus (i.v.) dose of 5 mg/kg. Subsequently, six cats were given [14C]azithromycin p.o. in a single dose of 5.4 mg/kg for the study of tissue distribution and metabolism. In both experiments, serial blood samples were collected and the plasma assayed for unchanged azithromycin to determine various pharmacokinetic parameters. After p.o. administration, bioavailability was 58% and absorption rapid with a tmax of 0.85 +/- 0.72 h and a Cmax of 0.97 +/- 0.65 microgram/mL. The harmonic mean terminal t1/2 after i.v. administration was 35 h. Tissue half-lives varied from 13 h in fat to 72 h in cardiac muscle. Three metabolites were identified in bile. Unchanged azithromycin accounted for 100% of the total radioactivity in lung and skin tissues when assayed. In comparison with other species, the bioavailability in cats is higher than in humans but lower than in dogs. As in the dog, > 50% of the azithromycin-related material in feline bile was unchanged azithromycin.

Absorption↗
PubMed1995

Estimating derivatives of pharmacokinetic response curves with varying bandwidths.

A kernel-smoothing method with locally varying bandwidths for the nonparametric estimation of derivatives of a function is proposed for highly nonequidistant data as they occur in pharmacokinetic response curves. We construct estimates having the particular property that the derivative estimates correspond exactly to the corresponding derivatives of the curve estimate even under locally varying bandwidth choice. The effects on the estimation of peak location (characteristic points) are investigated. In an example, characteristic points are estimated for a recently developed in vivo isotope dilution assay for vitamin A (retinol) nutritional status. The in vivo kinetics of appearance and disappearance of isotopically labeled retinol can be described with the proposed method.

Anticarcinogenic Agents↗
PubMed1995

Application of the modified relative dose response test to pregnant Indonesian women for assessing vitamin A status.

OBJECTIVE: To determine the prevalence of subclinical vitamin A deficiency (vitamin A inadequacy) in Indonesian pregnant women as assessed by the modified relative dose response test. DESIGN: Cross-sectional study of the vitamin A statuses of pregnant (second trimester) women randomly selected from ten different villages. SETTING: West Java, Indonesia. SUBJECTS: A group of 144 pregnant women recruited from the local health posts. INTERVENTIONS: Modified relative dose response (MRDR) test, serum retinol determination and gynecological examinations. RESULTS: The mean (s.d.) MRDR ratio was 0.039 +/- 0.031. Of the women tested, the vitamin A status of 17% was provisionally classified as being marginal (subclinically deficient) (MRDR ratio > or = 0.060), of 35% as being uncertain (MRDR ratio between 0.030 and 0.060) and of 48% as being satisfactory (MRDR ratio < or = 0.030). CONCLUSION: If the vitamin A statuses of the 'uncertain' group are also deemed to be unsatisfactory, approximately half of the pregnant Indonesian women tested could benefit from an increased intake of vitamin A.

Adolescent↗
PubMed1994

In situ screening assay for cell viability using a dimeric cyanine nucleic acid stain.

A rapid and sensitive assay is described for the determination of cell viability of adherent and nonadherent cells that can be performed in situ in 96-well microtiter plates using fluorescence plate scanners. The assay, based on dye exclusion, utilizes a plasma membrane-impermeable, dimeric cyanine dye (YOYO-1). YOYO-1 fluoresces brightly only when bound to nucleic acids. Cells are incubated with YOYO-1, and fluorescence is measured before and after the addition of detergent, which allows the dye to enter the cells. The fluorescence before detergent treatment originates from nonviable cells that have membrane damage and take up YOYO-1. The fluorescence after detergent treatment originates from all cells in the sample. The ratio of the two fluorescence values is used as an indicator of cell viability. The cell viability results of this microplate assay closely resemble those of dye exclusion studies by flow cytometry and are similar but not identical to those of the thiazolyl blue assay, which uses a metabolic indicator of cell death. Because the assay can be performed in situ, without removing the medium, disintegrated cells, cell aggregates, and cells that stick to culture vessel walls are all included in the measurement.

Benzoxazoles↗
PubMed1994

Comparison of vitamin A status assessment techniques in children from two Indonesian villages.

The vitamin A statuses of preschool-aged children without clinical eye signs of vitamin A deficiency in two villages near Bogor, West Java, Indonesia, were studied by the modified-relative-dose-response (MRDR) test and the conjunctival impression cytology (CIC) method. In the second village the relative-dose-response (RDR) test was also applied. Of the children examined, 71% in the first village (group 1, n = 75) and 36% in the second village (group 2, n = 83) fell below the third percentile of the WHO reference standard of weight-for-age. The following provisional cutoff values for inadequate vitamin A status in Indonesia were used: MRDR (> or = 0.06), RDR (> or = 20%), CIC (an abnormal impression in one eye). The percent abnormal values were as follows: group 1--MRDR 48%, CIC 51%; group 2--MRDR 12%, RDR 11%, CIC 5%. Thus, the indicators gave concordant results for the two populations but did not necessarily identify the same individuals at risk. The consistency of the RDR test was much improved by increasing the oral dose of 3.5 mumol and by retesting only after a 3-wk interval.

Administration, Oral↗
PubMed1994

Assessment of the vitamin A status in lactating and nonlactating, nonpregnant Indonesian women by use of the modified-relative-dose-response (MRDR) test.

The vitamin A statuses of two groups of Indonesian women were compared by using the modified-relative-dose-response (MRDR) test: 1) lactating, nonpregnant women of lower socioeconomic status (n = 64) and 2) better-educated, premenopausal, nonpregnant, nonlactating women (n = 14). At times from 3 to 6 h after dosing, the mean ratio of dehydroretinol to retinol (DR/R) in the serum was approximately threefold higher in the lactating women than in the control group, eg, 0.109 +/- 0.073 and 0.034 +/- 0.015, respectively, at 5 h. At a provisional DR/R cutoff of 0.06, the vitamin A statuses of 70% of the lactating women and of 7% of the control women were judged to be inadequate. Only 7% of the variability in abnormal MRDR ratios could be attributed to body weight. Both abnormal and normal responses were highly reproducible when performed 0.5-3.25 mo after the first test.

Administration, Oral↗
PubMed1994

Hypovitaminosis A: contemporary scientific issues.

Contemporary scientific issues relating to vitamin A can be divided into three groups dealing with metabolism, physiology, and public health and policy. Current metabolic issues include intestinal interactions with other nutrients and food components, the pathways and control of carotenoid metabolism, the mechanisms underlying transport homeostasis, the functions of binding proteins, the actions of nuclear receptors in gene expression, and the pathways, mechanisms and control of isomerization reactions. Contemporary physiologic issues include the role of retinoids in embryogenesis, mechanisms involved in vision, the role of vitamin A in the immune response, therapeutic applications of retinoids, and mechanisms underlying the toxicity of retinoids. Public health and policy issues include the effects of vitamin A on mortality and morbidity among children in various societies, appropriate means for the assessment of vitamin A status, and suitable criteria for setting recommended dietary intakes.

Animals↗
PubMed1994

Vitamins: the tortuous path from needs to fantasies.

The discovery of vitamins in the early 1900s, their chemical characterization and the clarification of their metabolic functions are sequential aspects of a brilliant chapter in the history of modern nutritional science. Despite our current knowledge about vitamins, inadequate vitamin status still abounds in the less industrialized world. With some vitamins, toxicity also poses a problem. The average daily amounts of dietary vitamins needed to maintain physiological functions in generally healthy persons is fairly well known. Nonetheless, new indicators of vitamin status and in vivo kinetic analysis should allow refinement of these values. The dietary intake of fruits and vegetables has been associated with a decreased risk of major chronic diseases, including cancer and cardiovascular diseases. The specific contributions of different components of the diet, including several vitamins, to this apparent protective effect is still uncertain. Factors besides diet that affect chronic diseases are lifestyle, genetics, medical awareness, and habits like smoking. Fantasies among generally healthy persons that large supplements of any single vitamin or combination of them, like some magical amulet, will significantly stave off ill health have captivated a sizable percentage of our population. Such beliefs can only be changed, if at all, by appropriate educational messages based on convincing scientific data.

Chronic Disease↗
PubMed1994

Enzymatic formation of 9-cis, 13-cis, and all-trans retinals from isomers of beta-carotene.

9-cis Retinoic acid is a highly preferred ligand for the nuclear retinoic acid receptor RXR. Although 9-cis retinoic acid can be formed from all-trans retinoic acid in vivo and in vitro, the nature of the isomerization process has not been defined. 9-cis-Retinoic acid might also be formed biologically from 9-cis beta-carotene, an isomer of beta-carotene commonly found in foods. We have observed that enzyme preparations of rat liver and intestine convert highly purified 9-cis beta-carotene (99.8%) to a mixture of 9-cis, all-trans, and 13-cis retinals. Highly purified all-trans beta-carotene (99.7%) and 13-cis beta-carotene (99%) are primarily converted to all-trans retinal. Several aldehyde dehydrogenases in tissues can convert retinal to retinoic acid. Although the rates of cleavage of 9-cis and 13-cis beta-carotenes are slower than that of the all-trans isomer, the oxidative conversion of 9-cis beta-carotene to 9-cis and all-trans retinals is the first identified enzymatic reaction for the formation of 9-cis retinal in animal tissues.

Aldehyde Dehydrogenase↗
PubMed1994

Infant mental health in occupational therapy practice in the neonatal intensive care unit.

The work of supporting an infant's emotional development and mental health begins in the neonatal intensive care unit (NICU). It depends on understanding the family and uses the parallel processes involved in relationship building to maximize the environment for the optimal development of the infant in the NICU. Occupational therapy service provision is discussed in light of knowledge about the developmental work of the full-term neonates and their parents and the corresponding work of infants in the NICU and their families. A brief vignette of occupational therapy services provided in the context of a relationship-focused infant mental health model is included.

Adult↗