Biomedical subjects

N M Jackson

Publications and source records attributed to N M Jackson.

8 recordsLinked to original sources

PubMed1996

Using pressure to decrease the pain of intramuscular injections.

The purpose of this study was to determine if applying pressure to the site for 10 sec prior to an intramuscular injection would reduce injection pain, an approach suggested by anecdotal observation and the gate control theory. The subjects were 93 patients who had dorsogluteal intramuscular injections of immune globulin at a county health department. Forty-eight received the pressure treatment and 45 received a standard injection in which no pressure was applied. Mean pain intensity on a 100-mm visual analogue scale, adjusted for differences in injection volume, was 13.6 mm for the experimental group and 21.5 mm for the control group (P = 0.03). The findings suggest that simple manual pressure applied to the site is a useful technique to decrease injection pain.

Adolescent↗

PubMed1988

Interactions of cyclosporine with renal proximal tubule cells and cellular membranes.

Cyclosporine-induced nephrotoxicity is a limiting factor in the clinical use of cyclosporine. Since the manner in which cyclosporine interacts with proximal tubule cells and their membranes may provide insight into the cellular pathophysiology of cyclosporine toxicity, experiments were undertaken to characterize the interactions of cyclosporine with proximal tubule cells, renal brush border membranes, and renal cortical mitochondria. Cyclosporine bound to isolated rat renal brush border membranes in a saturable manner with a Kd of 0.38 microM and an nmax of 0.33 nmoles/mg protein. Scatchard analysis suggested that the interaction of cyclosporine at low concentrations with brush border membranes was consistent with a partitioning process rather than binding to a specific membrane component. Cyclosporine inhibited rat renal cortical mitochondrial respiration in a dose-dependent manner, with 8 microM as a threshold dose. This inhibitory effect was greater for respiration supported by succinate than pyruvate-malate. TMPD-ascorbate-supported respiration was unaffected. Suspensions of rabbit renal proximal tubule segments were incubated in vitro with 0.5-500 microM 3H-cyclosporine to measure the kinetics of cyclosporine uptake. Uptake was rapid (80% after 10 min) and saturable at 100 microM, with 9 nmoles cyclosporine/mg protein accumulated. Incubation of suspensions of enriched in rabbit renal proximal tubule segments with 10 microM cyclosporine in vitro for 2 hr with or without 22.5 min of hypoxia, or for 16 hr without hypoxia, had no effect on a variety of quantitative metabolic parameters of cell injury, including basal and uncoupled tubule respiratory rates and tubule K+, Ca++ and adenine nucleotide levels. These results demonstrate that cyclosporine interacts with critical renal membrane components at low concentrations but this interaction does not result in proximal renal tubular cell injury acutely in vitro.

Adenosine Triphosphate↗

PubMed1988

Cyclosporine effects on isolated membranes, proximal tubule cells, and interstitium of the kidney.

The pathogenesis of renal cell injury is a complex interplay among derangements in subcellular membrane function and mediators of injurious processes. Plasma and subcellular membrane injury and the resulting membrane dysfunction appear especially important. As detailed previously in this report, Cs, an extremely lipophilic compound, has the ability to bind to renal brush border membranes, interact with mitochondrial membranes resulting in multiple sites of dysfunction, and accumulate in high concentrations in renal proximal tubule cells. In spite of these interactions, Cs could not be shown to be directly toxic in vitro to proximal tubule cells. Thus, from these experiments, it is difficult to conclude that Cs-induced acute renal failure observed in vivo is due to a direct tubular toxic effect, even though Cs has the capability to interact with critical renal membranes at low concentrations. The majority of present evidence, therefore, does not suggest a toxic effect of Cs on renal epithelial cells. Instead, the acute effect of Cs to produce a decline in renal excretory function appears to be due to a fall in renal blood flow. On the other hand, the chronic effect of Cs to produce a decline in renal excretory function appears to be due to an effect of this agent to induce interstitial fibrosis. In this regard, recent findings summarized in this report demonstrate that Cs produces (over ten days) a higher than normal collagen content, as measured by hydroxyproline levels, in the kidney. In addition, this increase in collagen content with Cs treatment was associated with a significant increase in proliferation of cells in the renal interstitium, as determined by 3H-thymidine incorporation into DNA. This increase in DNA incorporation after Cs was not observed in other organs, including liver, spleen, or heart. Histologic assessment of these proliferating cells revealed them to be mononuclear. Cell surface markers also demonstrated an increase in LCA positive cells in the renal interstitium. These results, therefore, suggest a readily demonstrable effect of Cs on the renal interstitium. The relationship between Cs dosage and interstitial cell proliferation as well as the relationship between Cs-induced renal perfusion alterations and this interstitial proliferative process mandates further investigation.

Animals↗

PubMed1987

Alterations in renal structure and function in a rat model of cyclosporine nephrotoxicity.

Adult male Sprague-Dawley rats maintained on a low sodium diet were administered 100 mg of cyclosporine per kg b.wt. per day s.c. for 4 to 10 days. Serum urea nitrogen was significantly elevated by day 4 and continued to rise, whereas serum creatinine was not elevated above control until day 10. Morphologic examination of perfusion-fixed kidneys from cyclosporine-treated rats revealed focal areas of tubular atrophy and interstitial fibrosis in the outer cortex and a generalized increase in interstitial cells in the outer medulla. No areas of acute tubular necrosis were identified. The effect of this dose of cyclosporine on renal hemodynamics was examined in conscious restrained rats. Renal blood flow, measured by microsphere injection, was 70% of control after four daily doses and remained near this level after eight daily doses. The glomerular filtration rate, measured by iodothalamate clearance, was 70% of control after four doses but fell to 34% of control after eight doses. [3H]Thymidine incorporation into renal DNA was used as a sensitive index of renal cell proliferation after cyclosporine administration (100 mg/kg/day). [3H]Thymidine incorporation was increased over control 3-fold in the outer cortex, 7-fold in the inner cortex and 11-fold in the medullary-papillary regions of the kidney after eight daily doses of cyclosporine. Histoautoradiographic examination of renal sections revealed an increase in the number of labeled nuclei in all three regions of the kidney from rats treated with cyclosporine. Morphometric analysis demonstrated that the majority of proliferating cells were located in the interstitium and not in renal tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Acute nephrotoxicity of 1,1-dichloroethylene in the rat after inhalation exposure.

A renal toxicity of 4 h inhalation exposure to 1,1-dichloroethylene (vinylidene chloride; VDC) was studied in male Sprague-Dawley rats. Kidney wt./body wt. ratios, serum urea nitrogen and creatinine levels were significantly increased 24 h after exposure to 250 ppm or more of VDC. Histopathologic examination by light microscopy of hematoxylin and eosin (H&E)-stained sections revealed severe tubular necrosis with calcium deposits at the higher exposure concentrations. Specific staining for calcium oxalate was negative, indicating that biotransformation of VDC to oxalate is probably not responsible for its nephrotoxicity. Pretreatment with polychlorinated biphenyl (PCB) induced the level of renal cytochrome P-450. Phenobarbital (PBT) pretreatment did not alter the renal P-450 level, but both PCB and PBT pretreatments antagonized VDC nephrotoxicity. These pretreatments have also been reported to antagonize VDC-induced hepatotoxicity. In summary, inhalation of VDC is nephrotoxic in the rat; the mechanism of nephrotoxicity does not involve calcium oxalate formation, and the magnitude of nephrotoxicity does not correlate directly with the total amount of renal cytochrome P-450.

Animals↗

PubMed1985

Pathogenetic mechanisms of nephrotoxicity: insights into cyclosporine nephrotoxicity.

Drugs may produce acute renal failure by prerenal, intrarenal and obstructive (postrenal) mechanisms. Prerenal processes usually develop from an imbalance of the normal counterbalancing vasoconstrictor and vasodilatory substances regulating RBF, resulting in a predominant vasoconstrictive state. Intrarenal processes develop from toxic renal tubule epithelial cell injury. The pathogenesis of renal cell injury is a complex interplay among derangements in subcellular membrane functions and mediators of injurious processes. Plasma and subcellular membrane injury and resulting membrane dysfunction appear most important. Cyclosporine has the ability to interact with renal tubular cell membranes in a relatively specific manner and at low concentrations. Despite this interaction, the acute declines in renal excretory function produced by cyclosporine is due predominantly to functional declines in RBF rather than structural derangements in renal tubular cell integrity. Cyclosporine-induced acute renal failure, thus, appears to be due predominantly to prerenal, rather than intrarenal, processes in the experimental animal. Cyclosporine does, however, possess a limited toxic potential to injure renal cortical cells, so that a chronic tubulointerstitial nephropathy may develop with long-term use of this immunosuppressive agent.

Acute Kidney Injury↗

PubMed1984

In vivo genotoxicity and acute hepatotoxicity of 1,2-dichloroethane in mice: comparison of oral, intraperitoneal, and inhalation routes of exposure.

The in vivo genotoxicity of 1,2-dichloroethane (DCE) was studied in the liver of male C57BL/6 X C3H F1 (hereafter called B6C3F1) mice after single p.o., i.p., and inhalation exposures. The acute hepatotoxicity of DCE was also examined in order to determine nonnecrogenic exposure levels for each route of administration. Single-strand breaks and/or alkali-labile lesions were demonstrated by alkaline DNA-unwinding/hydroxylapatite chromatography in hepatic DNA at 4 hr after p.o. or i.p. administration of nonnecrogenic doses (100 mg/kg, p.o.; 150 mg/kg, i.p.) of DCE to groups of four to six mice. No evidence of hepatic DNA damage was found immediately following 4-hr inhalation exposures of mice to a nonnecrogenic (150 ppm) or necrogenic (500 ppm) concentration of DCE. Four-hr inhalation exposures of mice to concentrations of DCE causing high mortality within 24 hr (1000 to 2000 ppm) produced evidence of hepatic DNA damage at 4 hr, but the possibility that this damage was due to the acute necrogenic effects of the exposures could not be excluded. A significant fraction of the hepatic DNA damage observed 4 hr after i.p. administration of DCE (200 mg/kg) was still evident after 24 hr, indicating the persistence of unrepaired lesions in the DNA. These findings are consistent with the seemingly contradictory results of the two long-term carcinogenicity bioassays, in which DCE was found to be carcinogenic to Osborne-Mendel rats and B6C3F1, mice when administered by gavage but nontumorigenic to Sprague-Dawley rats and Swiss mice after chronic inhalation exposure. Therefore, our results provide additional evidence for the importance of a route of administration effect in the in vivo genotoxicity and carcinogenicity of DCE.

Administration, Intranasal↗

PubMedDate not supplied

Electrochemistry of methylene blue bound to a DNA-modified electrode.

Gold surfaces have been derivatized with 15-base-pair double-stranded DNA oligonucleotides containing a pendant 5' hexanethiol linker. The electrochemistry of intercalated methylene blue has been investigated at these modified electrodes. Chronocoulometry, cyclic voltammetry, ellipsometry, and quantitation via 32P labeling are all consistent with a surface coverage of > or = 75% with the DNA helices stacked at an angle from the electrode surface. Cyclic voltammetry at low methylene blue/ duplex stoichiometries yields well-behaved surface waves with E degrees = -0.25 V (vs SCE), a value 0.03 V negative of that in aqueous solution. A binding isotherm for methylene blue at an electrode derivatized with the double-stranded sequence 5' SH-(CH2)6-p-AGTACAGTCATCGCG 3' was obtained from coulometric titrations and gave an affinity constant equal to 3.8(5) x 10(6) M-1 with a saturation value of 1.4(2) methylene blue intercalators per DNA duplex. Taken together, these experiments support a model for the surface morphology in which DNA duplexes are densely packed; methylene blue therefore reversibly binds to sites in the DNA that are close to the bulk solution. Electrochemistry at DNA-derivatized electrodes provides a valuable methodology to examine DNA-bound redox reactions and may offer new insight into DNA-mediated electron transfers.

DNA↗