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Biomedical subjects

J T Fleming

Publications and source records attributed to J T Fleming.

50 records · Page 3Linked to original sources
PubMed1987

Nitrendipine and the pressure-dependent vasodilation of vessels in the hydronephrotic kidney.

The influence of renal perfusion pressure on the vasodilation of the kidney caused by a calcium antagonist, nitrendipine, was studied. The diameter of several preglomerular and postglomerular vessels in the split hydronephrotic kidney of Inactin-anesthetized rats were measured by in vivo television microscopy. A reduction in the renal perfusion pressure to 80 mm Hg (femoral artery pressure) was achieved by clamping of the aorta above the renal arteries. The pressure reduction induced vasodilation of the arcuate arteries (proximal and distal), interlobular arteries (proximal and distal), and the afferent arterioles near the interlobular arteries. The afferent arterioles at sites near the glomerulus showed no pressure-dependent vasodilation. Topically applied nitrendipine led to a dose-dependent preglomerular vasodilation that did not further increase during perfusion pressure reduction. From these experiments, it is concluded that nitrendipine-induced renal vasodilation is independent of the renal perfusion pressure and primarily caused by its direct effect on preglomerular vessels.

Acetylcholine↗
PubMed1987

Comparison of the effects of antihypertensive drugs on pre- and postglomerular vessels of the hydronephrotic kidney.

The in vivo renal microvascular effects of three antihypertensive drugs: nitrendipine, a calcium entry blocker, and two direct-acting vasodilator agents, hydralazine and minoxidil, were compared. The dilator responses of pre- and postglomerular vessels were directly observed after the topical or intravenous administration of each drug using the hydronephrotic kidney preparation and television microscopy. When applied directly to the kidney to avoid changes in systemic blood pressure, all three drugs preferentially dilated the preglomerular vessels. The largest increases in preglomerular vessel diameters were observed with nitrendipine followed by hydralazine and minoxidil, in the order listed. These drugs produced little change in efferent arteriole diameters though acetylcholine evoked significant dilator responses of the same vessels. When infused intravenously to lower blood pressure, the predominant effect of the drugs was on the afferent arteriole. No significant changes in the efferent arteriole diameter were observed with any drug. These data demonstrate that these vasodilators, which act primarily at preglomerular sites, probably increase glomerular capillary pressure, but to differing degrees.

Administration, Topical↗
PubMed1987

The levamisole receptor, a cholinergic receptor of the nematode Caenorhabditis elegans.

We describe a glass fiber filter binding assay for the levamisole receptor, a putative acetylcholine receptor of the nematode Caenorhabditis elegans, and we show that receptor detected in vitro binds both levamisole derivatives and cholinergic agonists with the pharmacological specificity expected of the physiologically functional nematode receptor. The receptor is detected by the binding of tritiated meta-aminolevamisole ([3H]MAL, 27 Ci/mmol). In extracts of the wild-type nematode, there is a saturable, high affinity binding activity for [3H]MAL (Kd approximately 5-10 nM). Well fed wild-type worms contain as much as 3 fmol of high affinity binding activity per mg of extract protein (0.14 pmol/g of wet weight of worms) and dauer larvae, a special juvenile stage, contain as much as 15 fmol of activity per mg of protein. Specific binding activity per mg of protein is highest in larval stages and decreases severalfold in the adult worm. The rates of formation and dissociation of the [3H]MAL-receptor complex are relatively slow (dissociation half-life, 17 min), in agreement with physiological studies of levamisole on Ascaris muscle strips. Levamisole derivatives and cholinergic agonists have the same relative potencies in inhibiting [3H]MAL binding as they do in causing nematode muscle contraction. Vertebrate cholinergic antagonists do not inhibit [3H]MAL binding, but several antagonists (mecamylamine, alpha-bungarotoxin, and cobra venom) potentiate the binding of [3H]MAL and can be used to demonstrate more clearly the presence of a second, lower affinity binding activity whose ligand-binding affinity is also potentiated by these agents. Both high and low affinity wild-type binding components are missing in the extremely levamisole-resistant mutant unc-74(x19).

Age Factors↗
PubMed1986

Histamine-induced protein leakage in hypertensive rats: inhibition by verapamil.

Hypertension has been associated with an enhanced transport of macromolecules from the vasculature to the interstitium. The first objective of this study was to determine if, under control conditions, there is an enhanced leakage of macromolecules from the cremaster vasculature of the hypertensive rat. The second objective was to determine if the response to a mediator of macromolecular leakage (histamine) was altered in the renovascular hypertensive rat. A third objective was to determine if a calcium entry blocker, verapamil, could inhibit histamine-induced leakage and, if so, was the sensitivity to verapamil different in the renovascular hypertensive rat. Rats were anesthetized with pentobarbital, and the cremaster preparation was used for in vivo television microscopy studies. Fluorescein isothiocyanate was tagged to rat serum albumin (FITC-RSA), and the leakage of this albumin from the vasculature to the interstitium was quantitated by the use of fluorescent microscopy techniques. There was no difference during control conditions in macromolecular leakage between the normotensive and hypertensive rats. However, histamine induced a greater leakage in the renovascular hypertensive rat than in the normotensive controls. In addition, verapamil, in the presence of normal calcium levels, inhibited the histamine-induced leakage in the hypertensive rats but not in the normotensive controls. These data suggest that enhanced macromolecular leakage during hypertension may be due to an increased sensitivity to mediators of protein leakage. These agents may produce protein leakage by enhancing entry of extracellular calcium into endothelial cells.

Animals↗
PubMed1984

Mechanism of the biphasic arteriolar response to angiotensin II.

Male Sprague-Dawley rats (140-180 g) were anesthetized with alpha-chloralose and urethan. The cremaster muscle with intact blood supply and neural innervation was suspended in a tissue bath containing a modified Krebs solution. With the use of television microscopy the luminal diameters of third-order arterioles (14-32 micron) were measured before and after adding angiotensin II (ANG II, bath concn 10(-6) M). The arterioles responded to ANG II with an initial, transient constriction followed by a more prolonged dilation to a diameter larger than the control diameter. Pretreating the muscle with [Sar1, Ile8]ANG II significantly attenuated both the arteriolar constriction and subsequent dilation induced by ANG II. Treatment of the cremaster muscle with mefenamic acid or indomethacin, inhibitors of prostaglandin synthesis, produced a significant reduction in the diameter of the arterioles and abolished the dilator phase of the arteriolar response to ANG II without preventing the ANG II-induced constriction. These results demonstrate that within the intact microcirculation, ANG II produces both an arteriolar constriction and a dilation that are mediated by specific ANG II receptors. The ANG II-induced dilation of the arterioles appears to be caused by increased prostaglandin synthesis and release.

Angiotensin II↗
PubMed1982

Centrally mediated enhancement of ouabain cardiotoxicity by angiotensin II in dogs.

The effect of angiotensin II (Ang II) infusion on the doses of ouabain required to induce ventricular arrhythmias and death was investigated in anesthetized dogs. Tritiated ouabain was infused alone i.v. (1 microgram/kg per min) to establish the control toxic doses and the level of ouabain in the heart at death. When Ang II and ouabain were co-infused i.v. the doses of ouabain needed to induce arrhythmias and death were significantly reduced. Spinal transections performed at C-1 prior to drug infusions prevented the effect of Ang II to enhance the toxicity of ouabain. Thus, the action of Ang II to augment ouabain toxicity appeared to be related to its effects on the sympathetic nervous system. To confirm that Ang II was acting within the brain rather than at peripheral sites of the sympathetic system, Ang II was infused into the vertebral artery of spinal cord intact dogs. The infusion rate of Ang II needed to produce a significant enhancement of ouabain toxicity was much lower when given into the vertebral artery than into the femoral vein. These data indicate that Ang II enhances the cardiotoxicity of ouabain via an action produced within the brain and mediated by the sympathetic nervous system.

Angiotensin II↗
PubMed1982

Rapid and accurate direct injection chromatographic method for measuring volatile anesthetics in whole blood of dogs.

A modified rapid, accurate, and relatively simple gas chromatographic procedure was used for the analysis of a single hydrocarbon volatile anesthetic agent in whole arterial blood of dogs. Lengthy extraction procedures and laborious chromatographic separations were avoided. The glassware required was inexpensive and readily available, as were rubber and rubber-laminated Teflon septa which were excellent for making air-tight seals. Variations in blood pH, lipid content, protein concentration, hematocrit, and other components of whole blood will influence the solubility of the anesthetics. However, the procedure described in the present report was corrected for those factors by constructing standard curves with blood from each experimental dog. The arterial concentration of methoxyflurane (MTF) in 25 dogs was determined at 60 and 120 minutes of surgical anesthesia. Arterial concentrations of MTF at 60 minutes of anesthesia ranged from 7.29 to 41.7 mg/dl of blood, and at least 120 minutes, the range was from 9.02 to 55. There was no significant difference in arterial blood concentrations of MTF (P greater than 0.05) at 60 and 120 minutes of anesthesia.

Animals↗
PubMed1980

Serum inorganic fluoride and renal function in dogs after methoxyflurane anesthesia, tetracycline treatment, and surgical manipulation.

Effects of 2 hours of methoxyflurane-induced anesthesia in 25 dogs were determined by serum inorganic fluoride, serum urea nitrogen, serum creatinine, water intake, urine excretion, and urine specific gravity measurements; arterial concentrations of the anesthetic were also determined. The dogs were allotted to 5 groups (PTM, CTM, PTML, CTML, ML) of 5 dogs in each group and were anesthetized (M, in group designations) for 2 hours. The dogs were injected with chemically pure tetracycline or commercial tetracycline (PT and CT, in group designations) before, on the day of, and after anesthesia. In 3 groups, laparotomy (L, in group designations) was done; group ML did not receive tetracycline but a laparotomy was performed. Serum inorganic fluoride increased (P less than 0.05) in all groups 24 hours after anesthesia when compared with the base-line values; the highest mean serum concentration was 81.1 +/- 7.91 mumol/L (group PTM) and the lowest was 32.7 +/- 4.53 mumol/L (group PTML). There was no difference (P greater than 0.05) seen in serum urea nitrogen concentrations between groups. Methoxyflurane and tetracycline treatment caused no difference (P greater than 0.05) on serum concentrations of inorganic fluoride and urea nitrogen. Serum creatinine concentrations differed (P less than 0.05) only for groups PTM, CTM, PTML, and CTML vs group ML. Water intake reached peak at 48 hours after anesthesia. Arterial concentrations of methoxyflurane determined at 60 and 120 minutes of anesthesia indicated no difference (P greater than 0.05) among groups. Neither clinical nor laboratory signs of severe kidney dysfunction were detected in any of the experimental dogs during a 5-day observation period after anesthesia.

Anesthesia, Inhalation↗
PubMedDate not supplied

Molecular site assessment and process monitoring in bioremediation and natural attenuation. off.

A variety of modern biotechnical approaches are available to assist in optimizing and controlling bioremediation processes. These approaches are broad-ranging, and may include genetic engineering to improve biodegradative performance, maintenance of the environment, and process monitoring and control. In addition to direct genetic engineering strategies, molecular diagnostic and monitoring technology using DNA gene probing methods and new quantitative mRNA analytical procedures allows direct analysis of degradative capacity, activity, and response under in situ conditions. Applications of these molecular approaches in process developments for trichloroethylene (TCE), polychlorinated biphenyls (PCB), and polynuclear aromatic hydrocarbons (PAH) bio-oxidation in soils, aquifer sediments, and ground-water treatment reactors have been demonstrated. Molecular genetic technologies permit not only the development of new processes for bioremediation, but also new process monitoring, control strategies, and molecular optimization paradigms that take full advantage of vast and diverse abilities of microorganisms to destroy problem chemicals.

Bacteria↗
PubMedDate not supplied

Ferritin--a general metal detoxicant.

Binding of nonferrous metal ions to ferritin was compared to that of the phosphate-free or phosphate containing synthetic iron cores. The Scatchard plots for the synthetic cores reveal a high affinity site for Cd, Zn, Be, and Al, with KD in the range 10(-5)-10(-7) M. Preloading the cores with phosphate increased the number of metal ions bound without altering the KD. The metal ions with smaller ionic radii (Be, Al) were bound in larger numbers than those with larger ionic radii (Cd, Zn). Ferritin isolated from soybean (Glycina max), horse spleen, and rat liver bound the metal ions in amounts larger than predicted from their iron core. Whereas the iron cores and their nonferrous metal ion complexes were insoluble, those in the protein shell remained in solution. Thus apoferritin precipitated with lower concentrations of aluminum than did holoferritin. Also, Al bound to apoferritin reduced the rate of iron loading into the protein.

Animals↗
PubMedDate not supplied

Ferritin: the role of aluminum in ferritin function.

We previously showed that human brain ferritin (HBF) binds aluminum (Al) in vivo and in vitro and HBF isolated from Alzheimer's brain had more Al bound compared to aged matched controls (7). To further understand the role ferritin may play in Al neurotoxicity, we have studied in vitro the effect of Al on the function of human ferritin isolated from Alzheimer's (AD) and normal brain tissue, and compared the results with other mammalian ferritins. Al causes a concentration-dependent decrease in the initial rate of iron loading into apo-horse spleen and human brain ferritin and the rates were similar for ferritin isolated from both AD and normal brains. The rates of iron release of mammalian ferritins from different tissues were determined: horse spleen much greater than human liver greater than rat brain greater than human brain = rat liver ferritin. The rates of iron release of AD and normal human brain ferritin were similar and were unaffected by preloading with Al. Several mammalian ferritins were compared for their total iron uptake: horse spleen = human liver greater than human brain (normal) = human brain (AD) ferritin. In 20 mM HEPES (pH 6.0) buffer holoferritin is more resistant to precipitation by Al than apoferritin suggesting that holoferritin is a better chelator for nonferrous metal ions.

Aluminum↗
PubMedDate not supplied

Atrial natriuretic peptide causes pre-glomerular vasodilatation and post-glomerular vasoconstriction in rat kidney.

Atrial natriuretic peptide (ANP) can be extracted from rat hearts, and is found to increase fluid excretion by the kidneys when injected into test animals. The mechanism of ANP action is still unclear. ANP may reduce sodium reabsorption in the renal tubules, but it is also known that it increases the rate of glomerular filtration in the kidney, and relaxes preparations of smooth muscle, including one made from arteries that supply the kidney. To clarify its mode of action, we have studied directly the effects of semi-purified and synthetic ANP on blood vessels in the kidney of anaesthetized rats. We found that ANP causes a vasodilatation of the blood vessels which supply the glomeruli and a vasoconstriction of the arterioles which drain them. This substantiates the finding that increased filtration pressure participates in the natriuretic response.

Animals↗