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Biomedical subjects

B B Davis

Publications and source records attributed to B B Davis.

At least 163 records · Page 9Linked to original sources
PubMed1978

Impaired inner medullary production of prostaglandin E2 in the kidney of the myxedematous rat.

Renal cAMP concentration and renal prostaglandin (PG) E2 and PGF2alpha production were determined in control rats and rats with surgically induced myxedema. Slices from the kidneys of each group were incubated in vitro. cAMP concentration of inner medullary slices from the kidneys of myxedematous rats was decreased in comparison to slices from control rats. There was no difference between the two groups when slices from outer medulla and cortex were compared for cAMP level. In myxedema, there was decreased inner medullary production of PGE2, but not PGF2alpha. The difference in PGE2 production between myxedema and control rat kidneys was not corrected by addition of either arachidonic acid (170 micronM) or phospholipase A2 (5 microgram/ml). Arachidonic acid, however, increased inner medullary cAMP concentration in myxedema kidneys to a value not measurably different from control. Thus, there appears to be a decreased PGE2 production in the renal inner medulla of rats with myxedema. In view of the fact that PGE2 has previously been shown to increase inner medullary cAMP content, the reduced inner medullary content of cAMP would appear to be attributable to reduced PGE2 production.

Animals↗
PubMed1978

DDAVP (1-desamino-8-D-arginine-vasopressin) treatment of central diabetes insipidus--mechanism of prolonged antidiuresis.

DDAVP, 1-desamino-8-D-arginine-vasopressin, is a synthetic analog of arginine vasopressin which produces prolonged antidiuresis after intranasal administration to patients with complete central diabetes insipidus. We have studied the mechanism of the prolonged antidiuretic effect by specific radioimmunossay of DDAVP in plasma of patients and by in vitro studies on the adenylate cyclase-cylic AMP system of the rat outer renal medulla. When DDAVP was administredd to patients, all responded, but the duration of response among patients varied from 5-21 h. The peak level of DDAVP in plasma was achieved up to 4 h after administration indicating a slow absorption from the nasal mucosa. The disappearance time of DDAVP from plasma correlated significantly with the duration of antidiuresis, P less than 0.001. On a molar basis DDAVP was 3-fold greater than AVP in its stimulation of outer medullary adenylate cyclase activity and 10-fold greater than AVP in its stimulation of cyclic AMP content. The prolonged antidiuresis of intranasally administered DDAVP is due to slow absorption, presistence in plasma, and enchanced effect on the kidney.

Adenylyl Cyclases↗
PubMed1978

Kidney metabolism of acetaminophen and phenacetin.

The metabolism of acetaminophen and phenacetin by rabbit kidney slices was investigated. Phenacetin, like aspirin, inhibited [131I] Hippuran accumulation by the organic acid transport system. Phenacetin exhibited a dose-dependent inhibition with a K1 of 0.5 mM; acetaminophen at concentrations as high as 1 mM did not alter organic acid transport. [3H] acetaminophen slice: media ratios of approximately 1 or less suggested that acetaminophen entered cortex and outer and inner medullary slices by diffusion rather than active transport. Approximately 95% of the acetaminophen within the slices readily diffused out into the media. The chromatographic patterns of this material were similar to that of the incubation media. The acetaminophen remaining within the slices was acid-precipitable and not extractable with organic solvents. This covalent binding of acetaminophen was inhibited by glutathione. More acetaminophen was bound in the renal medullar than cortex. These data suggest that the renal metabolism of acetaminophen observed in this in vitro study may be related to the nephritis observed in analgesic abuse.

Acetaminophen↗
PubMed1977

Effect of oxygen and solute on PGE and PGF production by rat kidney slices.

Increasing oxygen from 5% to 95% resulted in an increases production of both PGE's and PGF's. The release of prostaglandins from slices of rat kidney cortex and outer and inner medulla was measured. Prostaglandin production was observed predominantly in the inner medulla, was close to the lower limit of detection in the outer medulla, and was undetectable in the cortex. Increasing oxygen concentration resulted in a threefold increase in inner medullary prostaglandin production. Synthesis at 95% O2 was less at 2100 mOsm than at 300 mOsm, while synthesis at 5% O2 was not affected by high solute concentration. The implications of these results with respect to kidney function are discussed.

Animals↗
PubMed1977

Prostaglandin E2 production by renal inner medullary tissue slices: effect of metabolic inhibitors.

Increasing oxygen from 5 to 95% has previously been shown to increase prostaglandin (PG) production in renal inner medullary slices. The possible role of oxidative phosphorylation in this process was investigated. The oxidative phosphorylation inhibitors, dinitrophenol (DNP), oligomycin, and cyanide were evaluted for their effects on PGE2 production and ATP levels. None of the inhibitors affected PGE2 synthesis, although they lowered ATP levels at the concentrations tested. In contrast, incubation of inner medullary tissue slices with 0% oxygen resulted in decreases both in PGE2 and ATP levels. This suggests that the effect of oxygen on prostaglandin synthesis may be due to substrate limiting effects rather than an effect on oxidative phosphorylation. When 22 mM 2-deoxyglucose was added to the incubation medium or when glucose was omitted, PGE2 levels increased. Sodium fluoride, presumably acting as a glycolytic inhibitor, increased PGE2 levels, with a maximal effect at 10 mM. ATP levels were 37% of control values with 20 mM NaF. This indicates that glucose may inhibit prostaglandin synthesis. These results indicate that oxygen (substrate) availability can limit inner medullary PGE2 production. In view of the low pO2 in the inner medulla, especially during antidiuresis, oxygen can potentially regulate prostaglandin production in this tissue.

Adenosine Triphosphate↗
PubMed1977

Effects of prostaglandins on rat renal adenylate cyclase-cyclic AMP systems.

The effects of prostaglandin (PG) E1, E2, A1, F1alpha, F2alpha or D2 on the rat renal cortical, outer medullary and inner medullary adenylate cyclase-cyclic AMP systems were examined. While high concentrations (8X10-4M) of each prostaglandin stimulated adenylate cyclase activity in each area of the kidney, PGE1 was the only prostaglandin to stimulate at 10-7M. PGA's were the only prostaglandins tested besides PGE's which stimulated adenylate cyclase at less than 10-4M. This effect of PGA's was limited to the outer medulla. PGD2 was the least stimulatory. Observations with renal slices yielded qualitatively similar results. The PGE's were the most potent in each area with PGA's only stimulatory in the outer medulla. O2 deprivation (5% O2) lowered the slice cyclic AMP content in each area of the kidney. In the cortex and outer medulla, prostaglandin mediated increases in cyclic AMP content were either lower or absent at 5% O2 compared to 95% O2. However, in the inner medulla PGE stimulation was observed only at 5% O2 and not 95% O2. No other prostaglandins were found to increase inner medullary cyclic AMP content at 95% or 5% O2. These results illustrate that the adenylate cyclase-cyclic AMP system responds uniquely to prostaglandins in each area of the kidney. Consideration of these results along with correlative observations suggests that inner medullary produced PGE's may act as local modulators of inner medullary adenylate cyclase.

Adenylyl Cyclases↗
PubMed1976

Mechanism of inhibition of organic acid transport in rabbit renal cortex by cyclic AMP.

The mechanism by which isoproterenol and cyclic AMP inhibit organic acid transport was examined. Accumulation of 131I-Hippuran (S/M) was used as an index of organic acid transport. Propranolol, an antagonist of isoproterenol's beta-adrenergic response, not only inhibited accumulation of Hippuran but, when combined with isoproterenol, caused further inhibition. PTH elicited larger increases than isoproterenol in cortical-slice cyclic AMP content but did not inhibit accumulation of Hippuran. This lack of correlation between a positive effect on the adenylate-cyclase-cyclic AMP system and inhibition of transport was also seen when other agents were tested. Cyclic GMP, which has been postulated to work in opposition to cyclic AMP, was as potent as cyclic AMP in decreasing S/M. The decreasing of S/M by adenine and uric acid could not be related to any known effect of these agents on tissue cyclic AMP content. Similarly, although 0.1 mM theophylline significantly decreased S/M, cortical cyclic-AMP content was not increased until a 100-fold greater concentration of theophylline was employed. The data suggest that the inhibitory effect of these agents was attributable to their molecular configurations, which interact directly with the organic acid transport system rather than indirectly via the adenylate-cyclase-cyclic AMP system.

Adenine↗
PubMed1976

Modulation of the cyclic AMP content of rat renal inner medulla by oxygen: possible role of local prostaglandins.

The lower O2 tension and more active anerobic metabolism that pertain in the inner medulla (IM) of kidney relative to cortex (C) are well recognized, but there is no evidence that O2 availability constitutes a limiting or regulatory factor in IM metabolism or function. In the present in vitro study, we examined the effects of O2 on adenosine 3',5'-monophosphate (cAMP) metabolism in slices of rat renal C and IM. After a 20-min incubation of slices in Krebs Ringer bicarbonate buffer with 95% O2 + 5% CO2 serving as the gas phase, the cAMP content of IM was 6-10 fold higher than that of C in either the presence or absence of 2 mM 1-methyl-3-isobutylxanthine in the incubation media. In slices of IM incubated for 20 min with 1-methyl-3-isobutylxanthine, cAMP was 22.5+/-SE 2.48 pmol/mg wet weight at 95% O2 and 4.37 without O2. Oxygenation of O2-deprived IM increased cAMP twofold in 2 min, an effect fully expressed in 5 min (fivefold increase). Further, cAMP of IM rose progressively and significantly over a range of atmospheric O2 content from 0 to 50% conditions which should reproduce and encompass O2 tensions that pertain in tissues in vivo. By contrast, basal cAMP content of C varied less than twofold in the presence of 95% versus no O2, implying that O2 modulation of cAMP was specific for IM. Indomethacin and meclofenamate, structurally distinct inhibitors of prostaglandin synthesis, both significantly decreased basal cAMP accumulation in oxygenated slices of IM but not of C. Meclofenamate also reduced basal adenylate cyclase activity determined in homogenates prepared from slices of IM which had been incubated at 95% O2. In slices of IM previously exposed to indomethacin or meclofenamate at 95% O2, a maximally effective concentration of exogenous prostaglandin E1 restored cAMP and adenylate cyclase activity to levels which approximated those observed at 95% O2 in the absence of an inhibitor of prostaglandin synthesis. These results suggest that O2 enhancement of cAMP content in IM may be mediated at least in part by local prostaglandins.

Adenylyl Cyclases↗
PubMed1976

"Bicarbonate resistant" metabolic acidosis in association with ethylene glycol intoxication.

A case of massive ingestion of ethylene glycol is described. The clinical characteristics of this disorder such as persistent metabolic acidosis and oxaluria as well as changes in serum osmolality that may accompany ingestion of certain toxins are emphasized. The rapid clearance of ethylene glycol from the blood during hemodialysis is noted and the use of ethyl alcohol to block metabolic conversion of ethylene glycol to oxalic acid, which is also a toxin, is described. The importance of early diagnosis and therapy is stressed.

Acidosis↗
PubMed1976

Interference with function of unipolar pacemaker due to muscle potentials.

One hundred and seventy-three unipolar pulse generator systems were tested in 169 patients to determine the incidence of sensing of muscle potentials. One hundred and twenty-two implants in the pectoral region were suitable for assessment and 60 (49 per cent) demonstrated sensing. Ventricular-inhibited units sensed muscle potentials in 69 per cent (47 of 78), with 9 patients complaining of related symptoms. Ventricular-synchronous units sensed in 30 per cent (13 of 34) with no patient manifesting symptoms.

Action Potentials↗
PubMed1975

Pronoun assessment: a free speech technique.

A study of the free speech pronoun usage of 15 normal and 15 language-delayed children showed that it is possible to distinguish between children at five different levels of language development by considering linguistically relevant pronoun properties. The discriminating measure considered the frequency of pronoun types as a percentage of the child's total utterances. It is suggested that eliciting child utterances in a free play situation with the principal caregiver provides a good language sample and has potential as a diagnostic method.

Age Factors↗
PubMed1975

Impaired renal response to parathyroid hormone in potassium depletion.

In potassium depletion, a possible alteration of the proximal tubular response to parathyroid hormone (PTH) was evaluated in rat kidney. 1) There were impairments of both phosphaturic and urinary cyclic AMP responses to PTH. The site of the impairment was further investigated by studying the PTH-dependent cycle AMP system in renal cortex. 2) There was a lesser increase of cyclic AMP concentration by PTH in potassium-depleted slices, indicating the lesser urinary cyclic AMP was due to the specific impairment of PTH-dependent cyclic AMP in the kidney. 3). The activation of adenylate cyclase by PTH was impaired , but phosphodiesterase activity was not affected by potassium depletion, indicating the impairment of cyclic AMP generation was due to inhibition of adenylate cyclase. 4) The phosphaturic response to dibutyryl cyclic AMP infusion was also significantly less in the potassium-depleted animals, indicating the step subsquent to the cyclic AMP generation is also impaired. All above results indicate that, in potassium depletion, the renal response to PTH is impaired, and the impairment is both within the step of cyclic AMP generation and after the cyclic AMP generation.

Adenylyl Cyclases↗
PubMed1975

Hypomagnesemia following the diuresis of post-renal obstruction and renal transplant.

Three unusual cases are described which demonstrated hypomagnesemia and symptoms resembling magnesium deficiency syndrome. The hypomagnesemia was most likely secondary to urinary losses from diuresis following release of post-renal obstruction and renal homotransplantation. Heretofore, this association has not been described. Case 1 was unique because of the post-obstructive diuresis in the face of marked renal impairment. Case 2 is noteworthy because of the profound hypomagnesemia, 0.4 mEq/1, and because of the development of congestive heart failure. The rapid improvement noted in cardiac function with magnesium replacement suggests a relationship to magnesium deficiency.

Adult↗