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Biomedical subjects

R E Howell

Publications and source records attributed to R E Howell.

52 records · Page 3Linked to original sources
PubMed1985

Captopril removal by rabbit lung in vivo.

Removal of [14C]captopril by the lungs of anesthetized rabbits was measured by the multiple indicator dilution technique. After coinjection of indocyanine green (ICG) and [14C]captopril into the jugular vein of anesthetized rabbits, serial blood samples were collected from the carotid artery and each was analyzed for its content of both substances. Percent removal (R) of captopril after its initial injection of 10 nmoles captopril/kg (calculated at the peak of the ICG outflow curve) was 40.2 +/- 2.5 (S.E.M.) and was significantly greater than R after a second injection of 10 nmoles captopril/kg (20.1 +/- 2.4) 1 hr later. Removal of 70 nmoles captopril/kg (5.8 +/- 3.0 after first injection, 6.4 +/- 2.2 after second injection) was significantly lower than R of 10 nmoles captopril/kg. During a single pulmonary passage of either dose of captopril, R was inversely related to the calculated fractional concentration of intravascular captopril. Pulmonary metabolism of the angiotensin converting enzyme (ACE) substrate [3H]benzoyl-Phe-Ala-Pro [( 3H]BPAP) was 70.1 +/- 1.7% in the absence of captopril, and was reduced significantly to 27.4 +/- 2.4% by 10 nmoles captopril/kg and 7.6 +/- 0.2% by 6 mumoles BPAP/kg. BPAP (6.4 +/- 0.6 mumoles/kg) significantly reduced R of the first and second injections of 10 nmoles captopril/kg but this effect was selective, since BPAP did not reduce pulmonary removal of [14C]serotonin. These data indicate that pulmonary removal of captopril in vivo is saturable and may primarily reflect binding of the drug to pulmonary endothelial ACE.

Animals↗
PubMed1985

Starch artifacts in oral cytologic specimens.

Starch powder from surgical gloves is a common artifact that may superficially resemble atypical epithelial cells or spores in oral cytologic specimens. This article describes the distinguishing features of starch granules visible under a light microscope and discusses their clinical relevance.

Cheek↗
PubMed1985

Histamine and secondary autoimmune infertility in dark mink (Mustela vison).

Testicular histamine content was higher in December (the time of sexual quiescence) that in March (breeding time) in opaline mink. Although testicular histamine synthesis increased in March over December, the increased cellular mass and increased histaminase activity prevented the biogenic amine from rising. Dark mink, however, had higher gonadal levels of histamine in March than in December owing to an increased rate of synthesis and a decreased rate of inactivation that correlated well with the onset of autoimmune infertility in this strain. Pastel mink were intermediate to the opalines, and dark mink indicative of strain differences in the genetic control of gonadal histamine synthesis and inactivation.

Amine Oxidase (Copper-Containing)↗
PubMed1985

Kinetics of captopril- and enalapril-induced inhibition of pulmonary angiotensin converting enzyme in vivo.

The kinetics of angiotensin converting enzyme (ACE) inhibition by captopril (SQ 14225) and enalapril (MK 421) in anesthetized rabbits was investigated. Kinetic parameters, apparent Km, an index of enzyme-substrate affinity and apparent Vmax, a measure of maximal rate of substrate conversion, were determined from indicator dilution measurements of single pass pulmonary metabolism of a synthetic ACE substrate [3H]benzoyl-phenylalanyl-alanyl-proline. Two methods for determination of kinetics in vivo from metabolism data were used. One fit pulmonary venous outflow metabolism data to a nonlinear model of saturable lung metabolic processes. This method required injection of sufficient substrate (benzoyl-phenylalanyl-alanyl-proline) to produce a large range of intravascular substrate concentrations. An alternative method required use of only low intravascular substrate concentrations. Both methods rely primarily on similar Michaelis-Menten assumptions and generated very similar results. Both captopril (10 and 20 nmol/kg) and enalapril (4 and 7 nmol/kg) behaved as noncompetitive ACE inhibitors in vivo. ACE inhibition was characterized by depressed [3H]benzoyl-phenylalanyl-alanyl-proline hydrolysis and apparent Vmax whereas apparent Km was unaffected. Other studies have suggested that these inhibitors act as competitive or mixed competitive and noncompetitive ACE inhibitors in vitro. Significant differences, however, between in vivo and in vitro experimental conditions suggest that the kinetics of enzyme inhibition in vitro may not necessarily reflect the action of the inhibitor in vivo. Additionally, results obtained in vivo may more accurately reflect the therapeutic behavior of these compounds.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Analysis of rabbit pulmonary angiotensin converting enzyme kinetics in vivo.

We investigated the kinetics of pulmonary angiotensin converting enzyme (ACE) in vivo by measuring the hydrolysis of a bolus dose of a synthetic ACE substrate, benzoyl-phenylalanyl-alanyl-proline (BPAP). Estimates of apparent Km and Vmax were calculated by multiple regression analysis using a nonlinear model of enzyme kinetics. A bolus injection of indocyanine green and BPAP was given into the jugular vein of anesthetized rabbits (3-4 kg b. wt.) and serial blood samples were collected at 1-sec intervals from the carotid artery. The concentration of indocyanine green, [3H]BPAP and its metabolite in each sample was used to construct pulmonary venous outflow concentration-time curves and to assess ACE activity. Addition of 0.04 to 2.6 mumol of unlabeled BPAP per kg to the injectate reduced [3H]BPAP metabolism in a dose-dependent manner, with a calculated ID50 of 0.37 mumol/kg at the peak of the outflow curve and 0.58 mumol/kg over the integral. There was a similar correlation between the concentration of BPAP in pulmonary blood, estimated from indocyanine green outflow curves, and the metabolism of [3H] BPAP. For each animal, application of the mathematical model provided statistically significant estimates of the kinetic constants for pulmonary BPAP metabolism in vivo. The apparent Km and Vmax were 9.3 +/- 0.8 and 63.1 +/- 9.5 mumol/sec/organ, respectively; the Vmax/Km was 6.8 +/- 1.0 ml/sec/organ. BPAP did not affect any of the hemodynamic parameters measured. The technique described provides a method for detailed study of the kinetics of pulmonary ACE in vivo and effects of inhibitor drugs or other experimental treatments on the function of this enzyme in the intact animal.

Animals↗
PubMed1983

Histamine H1 receptors and prostaglandin-histamine interactions modulating contractility of rabbit and rat testicular capsules in vitro.

The stimulatory effect of histamine on rabbit and rat testicular capsule was blocked by the H1 blocker, diphenhydramine, but not by the H2 blocker, cimetidine, suggesting the presence of H1 histamine receptors in both rabbit and rat testicular capsules. In the rabbit, both anti-prostaglandin F (PGF) and anti-prostaglandin E (PGE) effaced spontaneous autorhythmic contractions. They markedly inhibited PGF 2 alpha, PGE1 and histamine-stimulated contractions of the rabbit testicular capsule. In the rat, anti-PGF or anti-PGE had no inhibitory effects on the capsular tone, but they both inhibited the stimulatory effects of histamine. These data suggest that the action of histamine on the rabbit and rat testicular capsules could be due partly to a secondary release of the PG's, PGE2 and PGF2 alpha.

Animals↗
PubMed1982

Xanthine oxidase-induced lung injury inhibits removal of 5-hydroxytryptamine from the pulmonary circulation.

We were interested in determining the effect of lung injury initiated by superoxide anions and hydroxyl radicals on removal of 5-hydroxytryptamine (5-HT) and phenylethylamine by the isolated perfused lung. The rate of removal and percentage of removal of these bioamines was determined before and after lung injury initiated by perfusion of the lung with hypoxanthine (HX) and xanthine oxidase (XO) or xanthine oxidase alone for 10 or 30 minutes; free radicals are generated by such treatment. Because of variation in removal of bioamines among lungs of different animals, the effects of lung injury on bioamine removal were determined by calculating the percentage of inhibition of removal using data from the control and test period for each lung. Perfusion of the lung with HX/XO or XO for 10 or 30 minutes significantly inhibited 5-HT removal by 39.5% and 63.3%, respectively. In contrast, only perfusion of the lung for 30 minutes with HX/XO produced inhibition of phenylethylamine uptake (by 54.8%). As uptake of 5-HT is the rate-limiting step in 5-HT removal, these data demonstrate dose (time)-related depression of active 5-HT uptake by free radicals generated in vitro. The rate-limiting step of phenylethylamine uptake, metabolism by monoamine oxidase, is inhibited only by severe lung injury.

Animals↗
PubMed1982

The role of extracellular calcium in drug-induced contractile responses of the rabbit pulmonary artery.

Concentration-response relationships in rabbit pulmonary arteries to norepinephrine (NE), histamine (H) and potassium chloride (KC1) were determined in Ringer's solution containing 2.4, 1.2, 0.6, 0.1 or OmM CaCl2. The EC50 for NE and H did not vary with the extracellular calcium concentrations [Ca2+ ext], but the EC50 for KC1 was greatly increased in 0.1mM Ca2+. Maximum isometric contractile force in response to NE and H was significantly decreased in OmM Ca2+. Addition of 0.1 mM EGTA to the Ca2+-free solution further depressed the responses. KC1-induced maximum tension was decreased in 1.2mM, 0.6mM, 0.1mM and 0mM Ca2+. When a maximum concentration of NE (5 X 10(-5)M), H(5 X 10(-4)M) or KC1 (6 X 10(-2) was added to the bath the initial rapid phase of contraction induced by NE or H appeared to be dependent upon the release of internal Ca2+ from EGTA-sensitive and EGTA-resistant sites. The slow phase of contraction was dependent upon extracellular Ca2+. Both the fast and slow phase of contraction induced by KC1 (60 mM) was dependent upon extracellular Ca2+. In the presence of 0mM Ca2+ the tension response to NE (5 X 10(-5)M) was maintained, but the tension response to H (5 X 10(-4)M) was not maintained.

Animals↗
PubMed1982

Pineal gland - pituitary (alpha-MSH) interrelationships in fur priming and reproductive cycles in mink (Mustela vison).

Our investigations show that blindness, either natural or surgically induced results in a lack of fur priming and sexual development. Definite genetic color phase differences were observed in the sensitivities of the biological clocks for initiating fur priming, testicular development and time of breeding and whelping. Finely-bred dark mink molted and their pelts primed later in the fall than did either pastel or opaline mink. Testicular development was earlier and more extensive for the opaline, but was intermediate for the pastels and slower and least extensive for the finely-bred dark mink. The dark mink, however, bred earlier than did either the pastel and opaline strains. Hedlund (deaf, white) mink pelted about the same time as the pastels and opalines, but they bred and whelped later than the above three strains of mink. Plasma alpha-MSH levels were inversely related to testosterone levels and testicular development. It was high in all three strains (darks, pastels and opalines) during both the spring and autumnal molts, but was low during testicular development and breeding.

Animals↗
PubMed1980

Comparison of calcification between Bacterionema matruchotii and Actinomyces naeslundii.

The purpose of this research was to examine the requirements for proteolipid initiation of calcification in culture. Proteolipid from a calcifiable microorganism, Bacterionema matruchotii, was compared with proteolipid isolated from a non-calcifiable microorganism, Actinomyces naeslundii. Although A. naeslundii does not calcify in culture, lyophilized cells and proteolipid-containing extracts do initiate apatite formation. A. naeslundii proteolipid (ANN) differs from B. matruchotii (BMN) in concentration, apoprotein polarity, and phospholipid composition. These differences may alter the ability of ANN to nucleate apatite in the intact cell.

Actinomyces↗
PubMed1980

Alterations in pharmacological responses of rabbit skeletal muscle by reserpine pretreatment.

In the present study the isolated phrenic nerve-diaphragm preparation from rabbits pretreated with reserpine was used. Isometric twitch tension response was recorded. Concentration-response curves which demonstrated the neuromuscular blocking activity of d-tubocurarine were constructed. Curarized diaphragms were directly stimulated and concentration-response curves were made which demonstrated caffeine's ability to potentiate twitch tension. Pretreatment of rabbits with reserpine resulted in a potentiation of the effects of d-tubocurarine and caffeine. The present data indicate that pretreatment of rabbits with reserpine resulted in alteration of the in vitro responses of skeletal muscle to d-tubocurarine and caffeine.

Animals↗
PubMed1979

Fellowships offer expanded views of the health care world.

The authors briefly describe three fellowships that are currently available to health administration graduates. They also make some important observations about the usefulness of such fellowships and offer suggestions regarding fellowships in various key areas of the field of health care administration.

Education, Graduate↗
PubMedDate not supplied

Inhibition of antigen-induced pulmonary eosinophilia and neutrophilia by selective inhibitors of phosphodiesterase types 3 or 4 in Brown Norway rats.

Rolipram, a phosphodiesterase type 4 (PDE4)-selective inhibitor, has been demonstrated to inhibit antigen-induced pulmonary eosinophilia in guinea pigs and monkeys, suggesting that PDE4-selective inhibitors could be useful for treating asthma. Although the rat is used extensively in preclinical drug development, a pulmonary antiinflammatory effect of PDE4 inhibition has not been demonstrated in this species. Therefore, we examined the effects of rolipram, CI-930 (PDE3-selective inhibitor), zaprinast (PDE5-selective inhibitor) and aminophylline on antigen-induced pulmonary inflammatory cell influx in Brown Norway rats. Two weeks after sensitization rats were exposed to aerosolized ovalbumin and 24 h later bronchoalveolar lavage (BAL) was performed for determinations of total cell counts and cell type differentials. The resulting 10-fold increase in total cell counts was due primarily to an increase in eosinophils (from 0.06 to 11.0 x 10(6)) and neutrophils (from 0.02 to 12 x 10(6)). Rolipram, CI-930 and aminophylline, given p.o. before and after antigen challenge, each completely inhibited eosinophil influx, with B.I.D. ED50 values of 0.5, 0.4 and 39 mg/kg, respectively. Rolipram, CI-930 and aminophylline each completely inhibited neutrophil influx as well, with B.I.D. ED50 values of 0.1, 0.5 and 20 mg/kg, respectively. Denbufylline and milrinone (10 mg/kg p.o.) also inhibited eosinophil and neutrophil influx, consistent with PDE4 and PDE3 inhibition as the mechanisms of action of rolipram and CI-930, respectively. In contrast, zaprinast was inactive at 0.3-30 mg/kg. However, the beta2 agonist salbutamol greatly inhibited antigen-induced pulmonary eosinophilia and neutrophilia, with p.o. B.I.D. ED50 values of 2.1 and 2.3 mg/kg, respectively, indicating that drugs which increase intracellular cAMP levels by one of several mechanisms can inhibit antigen-induced pulmonary inflammation in rats. In conclusion, these results demonstrate that PDE4 inhibitors produce pulmonary antiinflammatory effects in rats. Furthermore, these results suggest that PDE3 inhibitors also can produce pulmonary antiinflammatory effects in vivo.

Aminophylline↗