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Biomedical subjects

T A Davis

Publications and source records attributed to T A Davis.

At least 109 records · Page 6Linked to original sources
PubMed1989

Orthostatic hypotension: therapeutic alternatives for geriatric patients.

Symptomatic orthostatic hypotension is a serious problem in the elderly because it can precipitate falls and fractures, myocardial infarctions, and strokes. Several disorders may cause symptomatic orthostatic hypotension including age-related changes in physiology, disorders of the autonomic nervous system, drugs, and a decrease in circulating blood volume. Orthostatic hypotension is defined as a fall in systolic pressure of at least 20-30 mm Hg and a fall in diastolic pressure of at least 10-15 mm Hg upon rising, with symptoms of cerebral ischemia. Management includes a search for reversible causes as well as nonpharmacologic and pharmacologic therapies. No single agent has been universally successful in relieving the symptoms of orthostatic hypotension. Trials of single agents or combinations of agents are needed to identify the most appropriate therapy for individual patients.

Aged↗
PubMed1989

Pharmacotherapy of allergic rhinitis.

The pathophysiology, clinical manifestations and diagnosis, and pharmacotherapy of allergic rhinitis are reviewed. Allergic rhinitis is an immunologically mediated disease initiated by an antigen-antibody reaction in sensitized persons. Clinical manifestations include nasal obstruction, rhinorrhea, itching of the nose and eyes, coughing, and sneezing and may be perennial or seasonal. Diagnosis is confirmed by challenging the patient with suspected allergens in skin-prick tests. Avoidance of offending allergens is the cornerstone of therapy. Antihistamines and decongestants provides only minimal relief when used alone and are more effective when combined with other agents. Two newer antihistamines, astemizole and terfenadine, lack the sedative and anticholinergic properties of older antihistamines. Intranasal corticosteroids are particularly effective in relieving symptoms; beclomethasone diproprionate and flunisolide do so without producing systemic adverse effects. Cromolyn sodium is effective in relieving nasal symptoms and is the prototype of a new noncorticosteroidal class of compounds termed antiallergy drugs. Drugs under investigation for the treatment of allergic rhinitis include histamine H2-receptor antagonists, nonsteroidal anti-inflammatory agents, anticholinergic agents, and beta-adrenergic receptor agonists. Immunotherapy is a helpful adjunctive treatment. Treatment with drugs may be necessary for those patients with allergic rhinitis who find it difficult or impossible to avoid the offending allergen. The severity of symptoms and the adverse effects of agents should be considered when individual therapeutic plans are being established.

Humans↗
PubMed1988

Resistance of protein and glucose metabolism to insulin in denervated rat muscle.

Denervated (1-10 days) rat epitrochlearis muscles were isolated, and basal and insulin-stimulated protein and glucose metabolism were studied. Although basal rates of glycolysis and glucose transport were increased in 1-10-day-denervated muscles, basal glycogen-synthesis rates were unaltered and glycogen concentrations were decreased. Basal rates of protein degradation and synthesis were increased in 1-10-day-denervated muscles. The increase in degradation was greater than that in synthesis, resulting in muscle atrophy. Increased rates of proteolysis and glycolysis were accompanied by elevated release rates of leucine, alanine, glutamate, pyruvate and lactate from 3-10-day-denervated muscles. ATP and phosphocreatine were decreased in 3-10-day-denervated muscles. Insulin resistance of glycogen synthesis occurred in 1-10-day denervated muscles. Insulin-stimulated glycolysis and glucose transport were inhibited by day 3 of denervation, and recovered by day 10. Inhibition of insulin-stimulated protein synthesis was observed only in 3-day-denervated muscles, whereas regulation by insulin of net proteolysis was unaffected in 1-10-day-denervated muscles. Thus the results demonstrate enhanced glycolysis, proteolysis and protein synthesis, and decreased energy stores, in denervated muscle. They further suggest a defect in insulin's action on protein synthesis in denervated muscles as well as on glucose metabolism. However, the lack of concurrent changes in all insulin-sensitive pathways and the absence of insulin-resistance for proteolysis suggest multiple and specific cellular defects in insulin's action in denervated muscle.

Adenosine Triphosphate↗
PubMed1988

Embryonic osmoregulation: consequences of high and low water loss during incubation of the chicken egg.

The rates of water loss of domestic chicken eggs were varied during incubation to measure the osmoregulatory ability of the avian embryo. Egg water loss was increased by drilling holes in the eggshell over the airspace on day 13 (I = 21 days) and then placing these eggs in a low relative humidity (r.h.: 0-10%) incubator until hatch. Egg water loss was decreased by placing other eggs in a high-r.h. (85-90%) incubator on day 0. Eggs with low water loss (approximately 6% of initial fresh mass [IFM]) produced embryos and yolks that were not different in wet or dry mass when compared to control eggs that lost approximately 12% of IFM. However, 1-4 gm of excess albumen were left in low-water-loss eggs on day 21. Hatching success was 71% and 89% for low and control eggs, respectively. Low egg water loss did not appear to disturb embryonic growth. The allantoic fluid volume and millimolar allantoic Na+ and Cl- ions declined faster with high and slower with low rates of water loss. Thus, excess water was lost as a result of increased movement of water out of allantoic fluid, which was due to increased active transport of Na+ ions by the chorioallantoic membrane (CAM). Eggs with high water loss had elevated Cl- levels after day 17 in plasma and amniotic fluid, which indicated a period of osmotic stress after depletion of allantoic fluid between day 18 and hatch. The decrease in wet embryo mass measured in embryos from high-water-loss eggs was due principally to dehydration of skin. Embryonic skin may serve as an emergency water reservoir during osmotic stress. Dehydrated chicks produced from high-water-loss eggs were 6 gm less in wet mass at hatch compared to controls. However, these chicks regained the water deficit 7 days after hatch and grew at a rate not different from control chicks through 6 weeks of age. Total egg water loss of 12% of IFM results in highest hatching success. However, water losses between 6% and 20% of IFM do not appear to affect adversely the growth or water content of the chick. Water losses above 20% of IFM cause early depletion of allantoic fluid, prolong the period of osmotic stress, and result in subsequent dehydration of blood, amniotic fluid, and embryonic skin.(ABSTRACT TRUNCATED AT 400 WORDS)

Allantois↗
PubMed1988

Long-term protein and calorie restriction: alterations in nucleic acid levels of organs of male rats.

The effects of dietary restriction (calorie and/or protein) imposed at weaning on tissue concentrations of nucleic acids and protein were determined in young (one year) and old (two year) rats. In liver, calorie restriction increased protein concentration and decreased RNA/DNA and RNA/protein, while protein restriction elevated liver DNA and reduced protein and protein/DNA. These changes are consistent with decreased liver cell size in response to protein, but not calorie, restriction. Age also influenced these parameters, since DNA (elevated), RNA/protein (elevated), protein (reduced), and protein/DNA (reduced) differed in livers of old as compared to young rats. In kidney, DNA concentrations were unaffected by age or dietary restriction. Although protein and nucleic acid concentrations are commonly used as baselines for expressing other biochemical parameters, our results indicate that in liver, these factors vary both with age and nutritional status.

Aging↗
PubMed1987

Exercise training ameliorates progressive renal disease in rats with subtotal nephrectomy.

To determine the effect of chronic exercise training on renal function in animals with moderate renal insufficiency, rats with 75% renal ablation were either exercise trained by swimming for two months or remained sedentary. Glomerular filtration rate was significantly higher in trained (1.89 +/- 0.07 ml/min) than in sedentary rats (1.52 +/- 0.11 ml/min). No change was observed in renal blood flow or the degree of hypertension. Proteinuria was reduced in trained (13.6 +/- 4.9 mg/24 hr) compared to sedentary animals (33.5 +/- 9.2 mg/24 hr). The degree of glomerulosclerosis was much less prominent in trained animals. Plasma, low-density lipoprotein cholesterol-levels and total triglycerides were reduced in trained compared to sedentary rats. This study suggests that chronic exercise training ameliorates the progression of renal disease and improves plasma lipids in rats with moderate renal insufficiency. The mechanism for this improvement in renal function appears to be independent of the influence of systemic blood pressure.

Animals↗
PubMed1987

Glucose metabolism in muscle of sedentary and exercised rats with azotemia.

Insulin resistance has been demonstrated in chronic renal failure patients and may be improved by exercise training, but the mechanisms have not been identified. In this study, the response of glucose uptake, glycogen synthesis, and glucose utilization via glycolysis (glycolytic utilization) to stimulation by insulin and/or acute exercise were determined in isolated muscles from rats with moderate renal insufficiency that were exercise trained or remained sedentary. Moderate renal insufficiency had no effect on the basal rate, insulin sensitivity, or insulin responsiveness of glucose uptake, glycogen synthesis, or glycolytic utilization in muscle. The enhanced insulin responsiveness of both glycogen synthesis and glucose uptake following acute exercise, noted in control animals, was less in rats with moderate renal insufficiency, but the enhanced basal rate and insulin sensitivity after exercise were unaffected by moderate renal insufficiency. Exercise training increased the insulin sensitivity and responsiveness of muscle glucose uptake and glycolytic utilization in rats with moderate renal insufficiency and in controls. The effects of acute exercise and exercise training on insulin responsiveness of glucose uptake were additive in controls but not in animals with moderate renal insufficiency. These findings are compatible with the concept that moderate renal insufficiency is associated with a postreceptor defect in insulin's action in muscle, detectable only following maximal stimulation of glucose transport by insulin and exercise, and partially correctable by exercise training.

Animals↗
PubMed1987

Insulin-stimulated protein metabolism in chronic azotemia and exercise.

To determine whether training reduces the acute catabolic stress of an exercise bout, control and azotemic rats, either exercise trained or untrained, were subjected to a bout of exercise or allowed to rest. Protein turnover was measured immediately following exercise in isolated muscles. Azotemia (no exercise) increased protein degradation; acute exercise (no azotemia) decreased protein synthesis. Protein catabolism was greatest in acutely exercised azotemic rats. Training reduced azotemia-induced and acute exercise-stimulated increase in protein degradation. To determine whether this improvement in protein metabolism by training was due to increased insulin sensitivity, the dose-response to insulin was determined. Resistance of protein synthesis or degradation to insulin was not observed in azotemic rats. Either acute exercise or training increased sensitivities of protein degradation and synthesis to insulin; training also increased responsiveness of protein degradation to insulin. Thus exercise training reduced the elevated muscle protein catabolism due to azotemia and/or acute exercise and enhanced the action of insulin on muscle.

Acute Kidney Injury↗
PubMed1987

The effect of recombinant GM-CSF on the recovery of monkeys transplanted with autologous bone marrow.

The regulatory function of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte production in vivo was evaluated in an autologous bone marrow transplantation model using rhesus monkeys. Monkeys were exposed to 9.0 Gy total body irradiation and then transplanted with 5.0 x 10(7) low-density bone marrow cells/kg. Alzet miniosmotic pumps were subcutaneously implanted to deliver rhGM-CSF at a rate of 50,400 U/kg/d. Minipumps, containing either rhGM-CSF or saline, were implanted between zero and five days after transplantation for seven days. Kinetic recoveries of peripheral blood cells after either saline or rhGM-CSF treatment were compared. Treatment with rhGM-CSF accelerated the recovery of neutrophils. Neutrophils in rhGM-CSF-treated animals recovered to 80% (3.4 x 10(3)/mm3) pre-irradiation control levels by day 20, in comparison with only 33% (0.9 x 10(3)/mm3) recovery for saline control monkeys. In addition, the recovery of neutrophils was enhanced over that of the controls, reaching 140% v 70% on day 30. Another prominent feature of rhGM-CSF-treated monkeys was the accelerated recovery of platelets, reaching near 50% normal levels by day 24 in comparison with 20% of normal levels for controls. The infusion of rhGM-CSF was shown to be an effective regulator of early hematopoietic regeneration, leading to the accelerated recovery of both neutrophils and platelets and then providing a consistent sustained increase of neutrophils even in the absence of rhGM-CSF.

Animals↗
PubMed1987

Effects of increased water loss on growth and water content of the chick embryo.

Domestic chicken eggs that lost 25.1% of their initial mass during incubation produced embryos with smaller wet masses than control eggs that lost 12.5% of their initial mass. However, water-stressed embryos did not differ from control embryos in dry body mass, indicating that water-stressed embryos were dehydrated. Yolk, albumen, heart, and gizzard wet and dry masses were not different between water-stressed and control groups during the last week of incubation. However, wet mass of the liver was significantly greater and that of the right leg significantly less in water-stressed embryos. Tarsometatarsal length, dry mass of the liver and right leg, and daily rates of oxygen consumption were not different between groups. Hatching success was 20.5% for water-stressed eggs and 85% for control eggs. These results show that increased egg water loss during the last week of incubation results in embryos that weigh less because they have a lower water content, not because they grow more slowly. The reduction in water content, with respect to the individual organs and body parts examined, is due primarily to a difference in leg tissue water content. We conclude that embryos do not alter their growth in response to a change in the amount of water available in the egg.

Animals↗
PubMed1986

Response of muscle protein turnover to insulin after acute exercise and training.

To determine whether the enhanced insulin-sensitivity of glucose metabolism in muscle after acute exercise also extends to protein metabolism, untrained and exercise-trained rats were subjected to an acute bout of exercise, and the responses of protein synthesis and degradation to insulin were measured in epitrochlearis muscles in vitro. Acute exercise of both untrained and trained rats decreased protein synthesis in muscle in the absence or presence of insulin, but protein degradation was not altered. Exercise training alone had no effect on protein synthesis or degradation in muscle in the absence or presence of insulin. Acute exercise or training alone enhanced the sensitivities of both protein synthesis and degradation to insulin, but the enhanced insulin-sensitivities from training alone were not additive to those after acute exercise. These results indicate that: a decrease in protein synthesis is the primary change in muscle protein turnover after acute exercise and is not altered by prior exercise training, and the enhanced insulin-sensitivities of metabolism of both glucose and protein after either acute exercise or training suggest post-binding receptor events.

Adenosine Triphosphate↗
PubMed1986

Dopaminergic mechanisms and motor function: characterization of D-1 and D-2 dopamine receptor interactions.

The effect of selective D-1 and D-2 dopamine receptor agonists (SKF 38393 and LY 171555, respectively) on motor function was studied in rats with unilateral, quinolinic acid-induced striatal lesions. Dose-dependent turning ipsilateral to the side of the lesion was elicited by LY 171555, but not by SKF 38393. When the drugs were given together, however, SKF 38393 was able to increase the total number (but not the duration) of turning induced by LY 171555 in a dose-dependent fashion. Furthermore, either alpha-methyl-paratyrosine pretreatment, a DA-depleting agent, or SCH 23390, a D-1 antagonist, inhibited the LY 171555-induced rotation, which would be restored by SKF 38393. These observations suggest that both the D-1 and D-2 dopamine receptor systems participate in the regulation of rotational behaviors in striatally lesioned rats with normosensitive DA receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

Glucose metabolism in epitrochlearis muscle of acutely exercised and trained rats.

Effects of insulin on glycogen synthesis (GS), glycolytic utilization (GU), and glucose uptake (GT) were studied in isolated epitrochlearis muscles from exercise-trained or sedentary rats during recovery from acute exercise or at rest. During the 1st h after acute exercise, the enhanced basal and insulin-stimulated GT was directed mainly toward replenishment of glycogen but basal GU was also increased. During the second through third hours after exercise, basal GS decreased but remained greater than rest and basal GU and GT returned to normal. Insulin sensitivity of these parameters was enhanced. Training alone reduced basal GS but enhanced insulin sensitivity of GT and GU. Training reduced the acute exercise-stimulated increase in basal and insulin sensitivity of GS during recovery from acute exercise, probably due to elevated glycogen stores. Thus recovery from acute exercise or training, either alone or in combination, enhances insulin stimulated GT in muscle; however, the increased glucose is primarily channeled toward GS after acute exercise, which is reduced by prior training and is directed to GU in trained animals either at rest or after acute exercise.

Animals↗
PubMed1985

Human pharmacokinetics of esorubicin (4'-deoxydoxorubicin).

The pharmacokinetics of esorubicin, a new anthracycline antibiotic, was investigated in conjunction with a phase I clinical trial. The drug was administered to 12 patients as an intravenous bolus at a dose of 20 to 40 mg/m2. All patients had normal renal and hepatic functions and no third space fluid accumulation. Plasma and urine samples were assayed by HPLC. The peak plasma concentration of esorubicin was 0.74 +/- 0.57 microM (mean +/- SE). Esorubicin disappeared from plasma according to a tri-exponential pattern with a terminal half-life of 20.4 +/- 7.3 hr. The area under the plasma concentration versus time curve was 0.64 +/- 0.31 microM x hr. Total body plasma clearance was 45.5 +/- 26.8 liter/min/m2 and the apparent volume of the central compartment, 41.0 +/- 24.8 L. A single metabolite, 4'-deoxydoxorubicinol, was detected in plasma. This metabolite was observed in 5 patients only and its mean peak concentration was 0.029 +/- 0.017 microM. The area under the plasma versus concentration time curve for 4'-deoxydoxorubicinol was 0.02 +/- 0.014 microM xhr. The urinary excretion of total fluorescence within 5 days of therapy was 7.3 +/- 1.3% of the administered dose. Esorubicin represented more than 80% of the excreted anthracyclines. As in plasma, 4'-deoxydoxorubicinol was the only metabolite detectable in urine. No correlation between the various pharmacokinetic parameters and drug-induced toxicity was observed in this small group of patients.

Antineoplastic Agents↗
PubMed1985

On the search for new anticancer drugs 14: the plasma pharmacokinetics and tissue distribution of spin-labeled thio-TEPA (SL-O-TT).

We defined the plasma and tissue concentrations and pharmacokinetics of SL-O-TT, a spin-labeled analog of thio-TEPA, in 35-44-g male Swiss Webster mice that had received spin-labeled thio-TEPA at a dosage of 10 mg/kg. Concentrations of spin-labeled thio-TEPA in ethyl acetate extracts of tissue and plasma were determined by gas-liquid chromatography and electron spin resonance spectroscopy. Plasma concentrations of spin-labeled thio-TEPA declined in a biexponential fashion that was well described by the equation: Ct = 21.5e-0.276t + 2.30e-0.026t indicating a half-life alpha of 2.5 min and a half-life beta of 26.6 min. After 2 h there was still spin-labeled thio-TE-PA in plasma, but not in tissues. In tissues, no spin-labeled thio-TEPA was detected with gas-liquid chromatography 15 min after injection, but with electron-spin resonance label was found in lung and skeletal muscle. The main metabolite of spin-labeled thio-TEPA is spin-labeled TEPA, where oxidative desulfurization is invoked as the main metabolic mechanism. Reduction of the spin label to the hydroxylamine was also observed with time.

Animals↗