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S Christensen

Publications and source records attributed to S Christensen.

230 records · Page 13Linked to original sources

Renal adaptations to continuous administration of furosemide and bendroflumethiazide in rats.

During continuous treatment with diuretics, the kidney adapts to the initial Na loss by activating antinatriuretic mechanisms which serve to prevent further Na and volume losses. To study the renal sites of adaptations to constant diuretic treatment, bendroflumethiazide (4 mg daily), furosemide (8 mg daily) or vehicle (0.24 ml daily) was infused intraperitoneally to female Wistar rats by implanted osmotic minipumps. Half of the animals (groups vol.) were randomized to receive a balanced saline solution to drink in addition to water in order to replace Na, K and volume losses. On the 6th day of treatment, clearances of inulin, Na, and Li were determined during four consecutive 6 hr periods. Circadian changes in renal excretions occurred in all groups with highest excretions of Na, Li and water in the dark period (6 p.m. to 6 a.m.). Renal changes induced by continuous infusion of diuretics were most pronounced in the dark period and would probably not have been disclosed if the clearance experiments had been restricted to the daytime. The average 24-hour clearance for inulin (glomerular filtration rate) was not different among groups, except for a 20% decrease in the furosemide group. The 24-hour fractional Na excretion, being approximately 0.5% in the vehicle group, increased to approximately 0.8% in group (bendroflumethiazide+vol) and to approximately 2.8% in group (furosemide+vol) but was not different from the vehicle group in the diuretic groups without volume replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Effects of recovery from anesthesia and surgery on renal sodium handling in conscious rats.

The accumulating evidence that the delivery of fluid from the proximal tubules to the loop of Henle (Vprox) can be measured in conscious rats by the lithium clearance (CLi) technique has renewed interest in developing a method by which also the glomerular filtration rate can be measured in conscious rats in a steady-state condition without influence from anesthesia and surgery. In the present study, Wistar rats of both sexes were put into a restraining cage, catheters were implanted in the jugular vein and the bladder, and renal parameters were determined under various conditions: different types of surgery, absence or presence of infusion with saline or glucose, normal or reversed diurnal rhythm, and examination at various times after surgery. In acutely operated and restrained rats given saline infusion, the proximal tubular fluid output (CLi) as well as the urinary excretion of sodium (UNaV) increased markedly during the first hours after anesthesia and surgery. After 5 h, both variables were significantly higher than in unoperated, unrestrained rats (CLi 364 +/- 40 vs. 151 +/- 38 microliters/min/100 g; UNaV 1,243 +/- 433 vs. 219 +/- 88 nmol/min/100 g; means +/- SD). Reversal of the diurnal rhythm did not change this pattern. Rats infused with 150 mM glucose instead of saline showed similar increases in CLi and UNaV, although the absolute levels were lower than in saline-infused rats. Rats given no infusion at all had subnormal values of CLi and UNaV. Rats operated 1-3 days before experiments and infused with saline showed enhanced although more stable values of CLi and UNaV.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia Recovery Period↗

Tetraethylammonium and p-aminohippurate as clearance markers for renal plasma flow in the rat during saline and glucose infusion.

Renal plasma clearances (C) of 14C-tetraethylammonium (TEA) and p-aminohippurate (PAH) as estimates of arterial renal plasma flow (ARPF) were evaluated in anesthetized rats during control conditions and during intravenous glucose infusion. Venous renal blood flow was measured directly by means of a servo-controlled pump, keeping the renal venous pressure constant. Arteriovenous extraction fractions (E = 1 - P(renal venous)/P(renal arterial)) for PAH averaged 88.3 +/- (SE) 0.8% in control rats and 82.0 +/- 0.9% in glucose-infused rats (p less than 0.001); E(TEA) averaged 92.0 +/- 0.6 and 90.1 +/- 0.6%, respectively (p less than 0.05). Under both experimental conditions, (C/E)PAH did not differ significantly from ARPF, while (C/E)TEA underestimated ARPF; the rate of extraction of TEA exceeded the rate of excretion by 15-20%, probably due to accumulation of TEA in renal tissue. It is concluded that, when corrected for E, C(PAH) is in general a more accurate estimate for ARPF than C(TEA). However, under conditions involving changes in plasma glucose levels C(TEA) may provide a better estimate of the effective renal plasma flow than C(PAH).

Animals↗

Effects of uninephrectomy and high protein feeding on lithium-induced chronic renal failure in rats.

Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Experience with once daily dosing of gentamicin: considerations regarding dosing and monitoring.

Plasma concentrations of gentamicin following a fixed dose of 240 mg once daily to patients with normal renal function were measured. The purpose was to establish guidelines to achieve a sufficiently high peak concentration with an appropriately low risk of accumulation. In 40 patients, 1-hour concentrations of plasma gentamicin had a median of 9.3 mg/l (range: 4.5-19.0 mg/l) and 9.7 mg/l (range: 3.6-14.6 mg/l) on days 1 and 3 of gentamicin treatment, respectively. Thirty-nine patients had 1-hour concentrations > 5 mg/l. The 1-hour concentrations varied considerably intra- and interindividually but showed a significant inverse correlation with body weight, surface area and the estimated endogenous creatinine clearance. The plasma gentamicin elimination half-life correlated significantly with age and inversely with body weight and creatinine clearance. There was no increase in the mean plasma creatinine from day 0 to day 4. No patients showed signs of nephrotoxicity, although 2 patients, both elderly and with low body weight, showed signs of beginning gentamicin accumulation. In conclusion, gentamicin treatment with the dose of 240 mg once daily in 3 days to adults with normal kidney function generally does not require adjustment or monitoring. However, the dose should be increased in young patients with an excessive body weight, and decreased doses are needed for old and underweight patients. Monitoring of trough plasma gentamicin concentration is not necessary with treatment duration of 3 days or less.

Adult↗

The costs of a Medicare prescription drug benefit.

This paper describes a preliminary cost estimate, prepared by the Congressional Budget Office (CBO), of President Clinton's 1999 prescription drug benefit proposal. The CBO estimated that the new benefit would increase net Medicare outlays by $136 billion between 2002 and 2009, although these estimates are highly uncertain. Because the proposal included an annual cap on the amount of the benefit, it did not require consideration of an important effect of a more comprehensive benefit: higher prices for some drugs. Estimates of future proposals for a Medicare prescription drug benefit may require consideration of that pricing effect.

Budgets↗

Alternatives for expanding health insurance coverage.

In March 1990, nearly 14 percent of the U.S. population was without health insurance. This article examines five approaches to increase coverage: tax credits for the purchase of private insurance; changes in the regulation of the private insurance market; additional requirements on employers to provide employment-based insurance; expansion of Medicaid to selected groups; and a universal public health insurance program. Coverage would be most improved under a universal public insurance plan, and least improved by regulatory changes in the private insurance market. Significant but incomplete increases in coverage could be achieved through either new employer mandates or expansion of Medicaid. A tax credit could increase coverage appreciably only if it was substantial relative to the cost of insurance, and even then most of the credits would go to those who would have purchased insurance anyway.

Data Collection↗

Conversion of a qualitative screening test to a quantitative measurement of urinary cystine and homocystine.

Qualitative urinary screening procedures were converted to quantitative methods for urinary cystine and homocystine based on the reactions between these amino acids and cyanide-nitroprusside reagents. Cystine and homocystine are quantified by the measurement of absorbances at 521 and 524 nm, respectively. Cyanide-nitroprusside reacts with both cystine and homocystine. However, in the presence of silver nitrate, only homocystine reacts to produce a magenta color. Following the cyanide-nitroprusside reaction, absorbance must be read within three minutes for cystine and immediately for homocystine. The stability of the absorption spectra has no apparent effect on these quantitative assays. Amino acid concentrations are expressed as ratios to creatinine, which tends to eliminate false negative results in dilute urine specimens. The normal urine value for cystine and homocystine combined is 66.8 +/- 52 (n = 50) mg per g creatinine. The normal value for homocystine alone is 29.9 +/- 16.8 (n = 24) mg per g creatinine. The simplicity of these procedures allows these quantitative methods to be used as screening tests for cystinuria and homocystinuria.

Amino Acids↗

Sequence dependent synergistic cytotoxicity between etoposide and fluoropyrimidines.

The cytotoxic interactions between etoposide and two fluoropyrimidines (FP), 5-fluorouracil (FUra) and 5-fluoro-2'-deoxyuridine (FdUrd), were determined in L1210 cells by soft agar clonogenic assay and in five human adenocarcinoma cell lines by colony growth assay. The administration of etoposide prior to FP resulted in synergistic cytotoxicity in L1210, HCT-8, Mia PaCa, MCF-7, and T47-D cells while the reverse sequence resulted in additive or antagonistic cytotoxicity in L1210, HCT-8, and Mia PaCa cells. Etoposide prior to FdUrd produced more DNA single strand breaks than expected in L1210 cells, while the reverse sequence produced fewer than expected. The sequence--dependent synergistic cytotoxicity of etoposide--FP correlates with relative DNA single strand break production in L1210 cells.

Animals↗

Studies of the pathogenesis of enteric E. coli infections in weaned pigs: bacteriological and immunofluorescent studies.

Qualitative and quantitative, bacteriological studies were performed on spontaneous cases of post weaning E. coli diarrhoea (PWD). The pigs derived from a herd, D, in which the disease had persisted for a period of almost 2 years. Orally vaccinated healthy pigs from herd D and from herds A and M without the disease were also examined. The results showed that haemolytic E. coli were frequently isolated from faecal samples which had been collected 5--7 days after weaning but seldom from samples from the same pigs collected before weaning. Haemolytic E. coli dominated the aerobic intestinal flora at 3--5 days after weaning in pigs from herd D with PWD. Oral vaccination using a formalinized vaccine delayed and suppressed the occurrence of haemolytic E. coli in pigs from herd D (Table I). Intestinal counts of the bacteria showed that the number of haemolytic E. coli present in the anterior portion of the jejunum was 10(-3)--10(-5) times higher in pigs which suffered from PWD than in weaned pigs of the same age which did not show symptoms of the disease (Table II). The lowest bacterial counts in various portions of the intestine were consistently observed in the sections obtained from the orally vaccinated healthy pigs. Pure cultures of K88-negative enteropathogenic E. coli serotype O149:K91 were consistently isolated from all the diseased pigs. Fluorescent antibody studies showed that the specific strain of bacteria adhered to the villous epithelium of the jejunum in a layer which covered the villi from the tip to the base and sometimes continued down into the crypts (Figure 1). The bacterial adhesion coincided with an intensive colonization of the jejunum with the homologous E. coli serotype and was nerve observed in apparently healthy pigs which did not have symptoms of PWD. It was concluded that characteristic intestinal colonization by adhesion may occur with enteropathogenic strains of E. coli O149:K91 which lack the K88 antigen (Figure 2).

Animals↗

Interaction of forskolin with vasopressin-sensitive cyclic AMP system in renal medullary tubules.

The medullary collecting tubules (MCT) and the medullary thick ascending limb of Henle's loop (MAL) are two major sites of [8-Arg]-vasopressin (AVP) action, via cyclic AMP, on the mammalian nephron. In the present study, the effect of forskolin and forskolin in combination with AVP on accumulation of cyclic AMP in tubular segments of MAL and MCT microdissected from rat kidney was examined in vitro. Under all tested conditions, forskolin stimulated the accumulation of cyclic AMP to a greater degree in MCT than in MAL. In MAL, the effects of forskolin and AVP were synergistic; the increase in cyclic AMP after incubation with forskolin and AVP added together was 150% greater than the arithmetic sum of the increases elicited either by AVP or by forskolin alone. On the other hand, in MCT the stimulatory effects of AVP and forskolin were strictly additive. These results suggest that an intramembranous arrangement of AVP-sensitive adenylate cyclase complex differs in two types of epithelial cells located in the same tissue. The potentiating effect of forskolin on AVP-stimulated cAMP generation in MAL can be helpful in experimental studies of AVP-sensitive cyclic AMP metabolism in this nephron segment, which has a variable sensitivity to AVP in the kidneys of diverse mammalian species.

Animals↗

Comparative and environmental genotoxicity of antimony and arsenic.

Antimony and arsenic compounds are known to have a genotoxic potential. Soil contamination with these elements can be due to the presence of natural ore sources of fahlore (gray copper). As a result, human and animal populations may be highly exposed. The sister chromatid exchange (SCE) test is an adequate tool for the sensitive detection of antimony and arsenic genotoxicity. We used this assay to investigate the coergism of the two elements in vitro to gain data for the assessment of a putative risk from coexposure. The combinative effect of antimony and arsenic in the SCE test appeared subadditive. Additionally, the SCE served to determine the genotoxic potential in extracts of contaminated fahlore soil samples gained under mildly acidic conditions. The genotoxicity observed was very low because antimony and arsenic predominated in the pentavalent, non-genotoxic state, but, the partial antagonism observed in the in vitro experiments could be an additional explanation for the low genotoxicity.

Adult↗