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Biomedical subjects

G A Porter

Publications and source records attributed to G A Porter.

At least 73 records · Page 4Linked to original sources
PubMed1985

Modification of experimental gentamicin nephrotoxicity by selective parathyroidectomy.

Dietary calcium loading reduces gentamicin nephrotoxicity in rats. Since parathyroid hormone increases renal brush border membrane anionic phospholipids, the putative gentamicin receptors, the effects of selective parathyroidectomy on gentamicin nephrotoxicity were examined. Male Fisher 344 rats underwent parathyroidectomy or sham surgery. All animals were fed a diet containing 0.5% calcium for 2 wk prior to gentamicin, 20 mg/kg twice daily for 6 and 10 days. Other parathyroidectomized rats were fed a 4% calcium diet for 2 wk and treated similarly with gentamicin On day 6, serum creatinine (mg/100 ml) was 2.0 +/- 0.9 in the sham-operated animals, 1.7 +/- 1.6 in the parathyroidectomized animals on the 0.5% diet, and 0.8 +/- 0.1 in the parathyroidectomized animals on the 4% diet. By 10 days, the sham-operated animals had creatinine values of 6.3 +/- 1.6 (mg/100 ml) compared with 1.7 +/- .9 in the parathyroidectomized animals on the same diet and 0.8 +/- 0.2 in the 4% diet animals. More severe tubular necrosis was present in the sham-operated compared with the parathyroidectomized animals. High calcium diet in the parathyroidectomized animals produced structural and functional protection from gentamicin nephrotoxicity. Human parathyroid hormone (1-34) 20 IU twice daily given subcutaneously to a separate group of parathyroidectomized rats, eliminated the protective effect of parathyroidectomy on renal structure and function. Parathyroidectomy modifies experimental gentamicin nephrotoxicity. The additional protective effect of dietary calcium loading may be independent of parathyroid ablation.

Animals↗
PubMed1985

Effect of amiloride on experimental gentamicin nephrotoxicity.

Potassium and magnesium deficiency have been reported as risk factors for experimental gentamicin nephrotoxicity. Amiloride, a potassium-sparing diuretic, also leads to increased renal magnesium reabsorption. Amiloride, 2 mg/kg/day, was given to groups of 8-12 Fischer 344 rats receiving gentamicin, 20 mg/kg b.i.d., for 3, 7, 10 and 14 days. Control animals received the vehicle for gentamicin, amiloride alone or gentamicin alone. The degree of renal failure and weight loss were similar in gentamicin and gentamicin + amiloride groups at all time points despite increases in serum potassium and magnesium in the amiloride-treated animals. Tubular dysfunction as assessed by depression of renal cortical slice uptake of p-aminohippurate and N-methylnicotinamide was not improved by the addition of amiloride. In addition, a comparable degree of tubular necrosis and regeneration was observed in all gentamicin-treated groups. Maximum gentamicin concentrations in the renal cortex did not differ. Thus, despite reduction of urinary losses of potassium and magnesium with resultant increased serum values, amiloride did not protect against experimental gentamicin nephrotoxicity. The tubular electrolyte wasting noted clinically is likely to be a result, rather than a cause of proximal tubular cell damage.

Amiloride↗
PubMed1984

Gentamicin-induced stimulation of DNA synthesis in rat kidney. Comparison between in vivo and in vitro models.

We have performed combined in vivo and in vitro measurements of thymidine uptake into kidney cortex DNA of animals treated with gentamicin for 7 days at 10 or 20 mg/kg daily (BID). Labelled thymidine is taken up by cortex fragments in vitro (90 min incubation) and incorporated into DNA; treatment of the animals with gentamicin results in a significant dose-dependent enhancement of this in vitro thymidine incorporation; labelled cells are found primarily in the proximal tubules and interstitium; there is an excellent correlation (r : 0.983, n = 15) between the changes of incorporation measured in vivo and in vitro as demonstrated by the sequential use of [3H]thymidine (in vivo) and [14C]thymidine (in vitro) within the same animals.

Animals↗
PubMed1983

Chronology of the sodium hypothesis and hypertension.

The observations that have provided the foundation of the sodium hypothesis of human hypertension are reviewed. Clinical observations made over 125 years ago initiated an investigative effort that has encompassed epidemiologic data, development of salt-related experimental models, and elucidation of theoretical mechanisms that interface Na+ balance with abnormal regulation of peripheral vascular resistance. In spite of the data available, a consensus is lacking on the relevance of applying the link between sodium intake and increased blood pressure in certain hypertensive patients to all persons.

Animals↗
PubMed1982

Effect of basis amino acids and aminoglycosides on 3H-gentamicin uptake in cortical slices of rat and human kidney.

The uptake of 3H-gentamicin was assessed in renal cortical slices of Fischer 344 male rats and four human cadaver kidneys not utilized for renal transplantation. In both species the uptake was maximal at 90 min and maintained a steady state thereafter. The characteristics of the energy-dependent component of 3H-gentamicin uptake were not altered by various basic amino acids, but competitive inhibition was induced by other aminoglycosides in a dose-dependent fashion. Thus aminoglycosides appear to share a transport process that is distinct from those of organic bases or other cationic substances. In addition, under the experimental conditions employed, the basolateral membrane of the tubular cell is capable of energy-dependent uptake of gentamicin. The role of this route of cellular uptake of aminoglycoside in clinical nephrotoxicity is speculative.

Amino Acids↗
PubMed1981

Nephrotoxic acute renal failure due to common drugs.

Antibiotics are the most common drugs implicated in clinical reports of drug-induced nephrotoxicity. The experimental basis for proposed mechanisms of acute renal failure in association with three groups of antibiotics--aminoglycoside, cephalosporin, and amphotericin B--are reviewed in detail. Proposed mechanisms of antibiotic-induced acute renal tubular necrosis involve either altering plasma membrane permeability or interference with cellular energy derived from mitochondria, For either aminoglycoside or cephalosporin antibiotics, cellular accumulation followed by interruption of mitochondrial respiration is the concept that has greatest support, although the possibility of an induced phospholipidosis involving intracellular lysosomes cannot be excluded. Altered renal tubular cell permeability due to the incorporation of amphotericin B into the pore structure of the plasma membrane is consistent with in vivo observation in either clinical or experimental examples of nephrotoxicity with this agent. The metal cis-platinum, used in treatment of neoplastic disease, has a clearly defined incidence of clinical nephrotoxicity with little insight as to cellular mechanisms. A possible mediation involving cis-platinum reducing the protein-bound sulfhydryl group of renal tissue has been proposed. With the ever increasing potency of modern pharmacologic agents come a rising risk of serious toxic side effects.

Acute Kidney Injury↗
PubMed1980

Pathogenesis of renal failure due to aminoglycosides and contrast media used in roentgenography.

The etiology of acute renal failure has changed in recent years due to the recognition of drug nephrotoxicity as a more common cause. In this communication we emphasize recent information concerning the pathophysiology of nephrotoxic acute renal failure produced by aminoglycoside antibiotics and the contrast media used in roentgenography. The aminoglycosides are excreted primarily by glomerular filtration; however, net tubular reabsorption and renal parenchymal accumulation do occur. The exact mechanism of uptake is not clear, but the luminal membrane seems primarily involved. The pathogenesis of nephrotoxicity, although probably linked to cortical accumulation, is complex since experimental animals recover from gentamicin-induced renal failure despite continued administration of the drug. Knowledge of the precise cellular mechanisms of injury awaits further studies. Histologic damage is usually limited to proximal tubular necrosis and, clinically, the renal failure is nonoliguric. Although reports of the contrast media used in roentgenography producing acute renal failure have increased, the pathogenesis is unclear. Evidence supporting various theories is reviewed.

Acute Kidney Injury↗
PubMed1980

Amikacin nephrotoxicity in the rat.

When amikacin was administered to Fischer rats at a dose of 120 mg/kg/day for up to 14 days, renal proximal tubule cells became vacuolated, but BUN and creatinine remained normal. Renal cortical drug levels rose steadily throughout the treatment period. When, in a second trial of the same duration, the drug dose was tripled, focal proximal tubular necrosis, then regeneration, occurred and the animals became azotemic. Tissue drug concentrations peaked and began to decline during the treatment period, having reached levels more than three times higher than achieved at the lower dose. Ultrastructural changes were similar to those observed with other aminoglycosides. The results indicate that amikacin is less nephrotoxic than gentamicin and more toxin than tobramycin and netilmicin in the Fischer rat.

Amikacin↗
PubMed1980

Effect of sodium bicarbonate and ammonium chloride ingestion in experimental gentamicin nephrotoxicity in rats.

To examine the possibility that gentamicin binding to renal tubular epithelium is electrostatic, the effect of sodium bicarbonate-induced alkaline diuresis and ammonium chloride administration on the course of gentamicin nephrotoxicity in male Fischer 344 rats was examined. After 14 days of gentamicin, sodium bicarbonate drinking animals did not differ significantly from tap water drinking controls in the degree of nephrotoxicity as determined by serum creatinine, in vitro para-aminohippurate and N-methylnicotinamide uptake, histology and renal cortical gentamicin concentrations. However, 7/10 sodium bicarbonate drinking animals had extensive intratubular renal calcifications as compared to 0/29 tap water drinkers. Ammonium chloride drinking animals had more severe toxicity than tap water drinking controls. We conclude that in our model, sodium bicarbonate administration does not reduce experimental gentamicin toxicity and is associated with intratubular calcification. Ammonium chloride potentiates gentamicin nephrotoxicity.

Ammonium Chloride↗