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  • 1
    ISSN: 1432-0738
    Keywords: Toxicity of Caffeine ; Toxicity of Nitrite ; Toxicity of Isophthalanilide ; Toxicity of Mercaptopurine ; Growth Rate of Rats ; Methemoglobinemia in Rats ; Hemolytic Anemia in Rats ; Stained Urinary Cells ; Renal Functions in Rats ; Red Blood Cell Counts in Rats ; White Blood Cell Counts in Rats ; Urinary Dilution ; Clearance of Free Water ; Osmolar Clearance ; Maximal Urinary Osmolarity ; Proteinuria in Rats ; Hemolysis Induced by i.v. Water ; Coffein: Toxicität ; Caffeinum: Toxicität ; Nitrite: Toxicität ; Isophthalanilid: Toxicität ; Mercaptopurin: Toxicität ; Wachstumsgeschwindigkeit von Ratten ; Methämoglobinämie bei Ratten ; Hämolytische Anämie bei Ratten ; Gefärbte Harnsedimente ; Nierenfunktionen der Ratte ; Erythrocyten: Zahl bei der Ratte ; Leukocyten: Zahl bei der Ratte ; Harnverdünnungsmechanismus ; Clearance des freien Wassers ; Osmotische Clearance ; Maximale Harnosmolarität ; Proteinurie bei der Ratte ; Hämolyse durch i.v. Wasserinjektion bei der Ratte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die allgemeine und renale Toxicität von großen Dosen von Phenacetin, Paracetamol und potentiell nephrotoxisehen Antimitotica, sowie anderen üblichen Bestandteilen von analgetischen Mischpräparaten wurde an Ratten in 30–60 Tage-Versuchen untersucht. Phenacetin und Paracetamol hemmten Futteraufnahme und Wachstum. 800–1200 mg/kg · Tag Paracetamol tötete mehr Tiere als 1500–3000 mg/kg · Tag Phenacetin. Die beiden Analgetica und das Antimitoticum Isophthalanilid riefen hyperchrome Anämie hervor. Phenacetin verursachte mehr Methämoglobinämie als Paracetamol. Weder dieser Analgetica, noch Coffein, noch Natriumnitrit, noch Isophthalanilid, noch Mercaptopurin verringerten das Glomerulusfiltrat, die maximale Harnkonzentrierungsfähigkeit nach Durst unter Vasopressin, die Harnverdünnuungsfähigkeit nach hypotonischen Infusionen oder die renale H+-Ionen-Sekretion. Phenacetin, Paracetamol und Isophthalanilid verringerten die fraktionelle renale Harnstoffausscheidung. Sehr große Dosen von Paracetamol steigerten leicht die Proteinurie und die Ausscheidung von Tubuluszellen im Harn. Phenacetin und Paracetamol verursachten degenerative Veränderungen im histologischen Bild der corticalen, proximalen und distalen Tubuli, die unter Blindbedingungen untersucht wurden. Es traten weder entzündliche Veränderungen, noch Schädigungen des Nierenmarks oder der Papille auf. Die corticalen degenerativen Veränderungen ließen sich nicht als Folge von Methämoglobinämie oder Hämolyse erklären. Isophthalanilid verursachte eine „Normalisierung” des histologischen Bilds der Nierenrinde über die Norm hinaus. Die Ausscheidung von Tubuluszellen im Harn war nicht signifikativ mit der Schwere der histologischen Veränderungen korreliert. Die Befunde führen zum Schluß, daß weder Phenacetin, noch Paracetamol bei der Ratte ausgeprägte nephrotoxische Wirkungen besitzt.
    Notes: Abstract The general and the renal toxicity of large doses of phenacetin, paracetamol, some antimitotic drugs and other constituents of analgesic mixtures was investigated in medium term toxicity tests in a large number of rats. Phenacetin and paracetamol depressed food intake and retarded growth. 800–1200 mg/kg · day paracetamol induced a larger mortality than 1500–3000 mg/kg · day phenacetin. Both analgesics and isophthalanilide, an antimitotic agent, induced hyperchromic anemia. Phenacetin induced methemoglobinemia more readily than paracetamol. Neither the analgesics, nor caffeine, sodium nitrite, isophthalanilide or mercaptopurine depressed GFR, maximal urinary concentration after dehydration plus vasopressin, urinary dilution after hypotonic expansion, or urinary acidification. Phenacetin, paracetamol and isophthalanilide depressed the fractional excretion of urea by the kidney. Very large doses of paracetamol slightly increased the proteinuria and the urinary excretion of tubular cells. Phenacetin and paracetamol induced degenerative histological alterations in cortical proximal and distal tubules, detected and quantitated under blind conditions. There were no inflammatory changes, nor any medullary or papillary lesions. The degenerative lesions could not be explained by the presence of methemoglobinemia or hemolysis. Isophthalanilide actually “improved” the histological appearance of the kidneys. The urinary excretion of tubular cells was not significantly correlated with the severity of the histological changes. It was concluded that neither phenacetin nor paracetamol exert major nephrotoxic effects in rats.
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  • 2
    ISSN: 1433-2965
    Keywords: Bone mineral density ; Dual-energy X-ray absorptiometry ; Lumbar vertebrae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The bone mineral density (BMD) of lumbar vertebrae in the anteroposterior (AP) view may be overestimated in osteoarthritis or with aortic calcification, which are common in elderly. Furthermore, the risk of spinal crush fracture should be more closely related inversely to the BMD of the vertebral body than to that of the posterior arch. Therefore, we measured BMD of lumbar vertebrae in lateral (LAT) view (L2–L3), using a standard dual-energy X-ray absorptiometer (DEXA), thus eliminating most of the posterior spinal elements. The precision of BMD LAT measurement was determined both in vitro and in healthy volunteers. Then, we compared the capability of BMD LAT and BMD AP scans for monitoring bone loss related to age and for discriminating the BMD of postmenopausal women with nontraumatic vertebral fractures from that of young subjects. In vitro, when a spine phantom was placed in lateral position in the middle of 26 cm of water in order to simulate both soft-tissue thickness and X-ray source remoteness, the coefficient of variation (CV) of six repeated determinations of BMD was 1.0%. In vivo, the CV of paired BMD LAT measurements obtained in 20 healthy volunteers after repositioning was 2.8%. The age-related difference between a peak bone mass group estimated in a group of 27 healthy women aged 20 to 35 years and a group of 50 women aged 60 to 75 years, in whom neither vertebral fracture nor osteoporosis risk factors could be detected, were 21.7% and 37.6% in AP and LAT view, respectively. An arbitrary BMD fracture threshold was defined in AP and LAT views as the 90th percentile of the BMD value of a group of 22 osteoporotic women with vertebral fractures. The distribution of BMD AP and LAT above and below this threshold in 169 consecutively screened women without vertebral fracture was then analysed. In both AP and LAT views, 39.1% and 31.3% had BMD values above and below this threshold, respectively. Of the remaining, 16.0% had a BMD below this threshold only in AP and 13.6% only in LAT view. Thus, if BMD LAT was a better reflection of vertebral body bone mass than BMD AP, and thereby a better predictor of the resistance to crush fracture, our results would suggest that only the use of the standard AP view could under- or overestimate spinal fracture risk in about 30% of women screened for osteoporosis. In conclusion, our results indicate that BMD measurement in lateral view is feasible with a standard DEXA instrument. This mode of scanning, besides overcoming artefacts due to osteoarthritis of the posterior arch and aortic calcifications, appears to provide a greater sensitivity for assessing bone mass loss of the vertebral body than the standard anteroposterior scan.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Osteoporosis international 4 (1994), S. S7 
    ISSN: 1433-2965
    Keywords: Bone fragility ; Bone mineral density ; Bone size ; Cortical bone ; Osteoporosis ; Puberty ; Sex difference ; Statural height ; Trabecular bone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Peak bone mass, which can be defined as the amount of bony tissue present at the end of the skeletal maturation, is an important determinant of osteoporotic fracture risk.Measurement of bone mass development. The bone mass of a given part of the skeleton is directly dependent upon both its volume or size and the density of the mineralized tissue contained within the periosteal envelope. The techniques of single-1 and dual-energy photon or X-ray absorptiometry measure the so-called ‘areal’ or ‘surface’ bone mineral density (BMD), a variable which has been shown to be directly related to bone strength.Bone mass gain during puberty. During puberty the gender difference in bone mass becomes expressed. This difference appears to be essentially due to a more prolonged bone maturation period in males than in females, with a larger increase in bone size and cortical thickness. Puberty affects bone size much more than the volumetric mineral density. There is no significant sex difference in the volumetric trabecular density at the end of pubertal maturation. During puberty, the accumulation rate in areal BMD at both the lumbar spine and femoral neck levels increases to four- to sixfold over a 3-and 4-year period in females and males, respectively. Change in bone mass accumulation rate is less marked in long bone diaphyses. There is an asynchrony between the gain in statural height and bone mass growth. This phenomenon may be responsible for the occurrence of a transient period of a relative increase in bone fragility that may account for the pattern of fracture incidence during adolescence.Variance in peak bone mass. At the beginning of the third decade there is a large variability in the normal values of areal BMD in the axial and appendicular skeleton. This large variance, which is observed at sites particularly susceptible to osteoporotic fractures such as lumbar spine and femoral neck, is barely reduced after correction for statural height, and does not appear to increase substantially during adult life. The height-independent broad variance in bone mass develops during puberty at sites such as lumbar spine and femoral neck, where the accretion rate is markedly increased.Time of peak bone mass attainment. Despite the fact that a majority of studies did not indicate that bone mass continues to accumulate significantly during the third and fourth decades, it has been generally accepted that peak bone mass at any skeletal site is attained in both sexes during the mid-thirties. However, recent studies indicate that in healthy Caucasian females with apparently adequate intakes of energy and calcium, bone mass accumulation can virtually be completed before the end of the second decade, for both lumbar spine and femoral neck. It is possible that both genetic and environmental factors could influence the time of peak bone mass achievement.Determinants of peaks bone mass. Several variables, more or less independent, are supposed to influence bone mass accumulation during growth; heredity, sex, dietary components, endocrine factors, mechanical forces, and exposure to risk factors. Quantitatively, the most prominent factor appears to be the genetic determinant, as estimated by studies comparing monozygotic and dizygotic twins. That heredity is not to be the only determinant of peak bone mass is of practical interest, since environmental factors can be modified. With respect to nutrition, the quantitative importance of calcium intake in bone mass accumulation during growth, particularly at sites prone to osteoporotic fractures, remains to be clearly determined. The same can be said for the impact of physical activity. Finally, the crucial years when these external factors will be particularly effective on bone mass accumulation remain to be determined by longitudinal prospective studies in order to produce credible and well targeted recommendations for the setting up of osteoporosis prevention programs aimed at maximizing peak bone mass.
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  • 4
    ISSN: 1433-2965
    Keywords: Epidemiology ; Hip fracture ; Osteoporosis ; Proximal femur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fracture of the proximal femur (hip fracture) as a consequence of osteoporosis is an important public health problem. Its incidence, which rises with age, varies according to geographical location and race. There is no information concerning hip fracture in Switzerland, which is a Western country with a particularly aged population. During 1987, 361 patients with hip fracture were recorded in the University of Geneva Hospital, which is the main referral center for a population of about 376000 inhabitants. This represented 94% of all hip fractures occurring in the region. A moderate trauma was reported in 329 cases (91.1%). The overall annual incidence was 96.1 per 100000 population (146.9 for women and 39.8 for men). When only hip fractures following moderate trauma were considered, the incidence was 87.6 per 100000 population (138.8 for women and 30.8 for men). Rare under the age of 65, hip fracture incidence increased exponentially in older subjects. The mean age of patients with hip fracture was 82.0 years in women and 75.7 years in men. The ratio of cervical to trochanteric fracture was 1.03 and 1.12 in women and men, respectively. The mean length of stay in the orthopaedic ward was 30.5 days, and the total costs amounted to 8.8 million Swiss francs for hip fracture associated with moderate trauma. Forty-seven percent of subjects were transferred to another hospital for recovery or rehabilitation. During the stay in the orthopaedic ward, the mortality rate was 8.2%. These results emphasize the high incidence and cost of hip fractures in a region of Switzerland where the population is particularly old. The problem could even worsen with the progressive aging of the population.
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  • 5
    ISSN: 1433-2965
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 6
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Währendl-val-Angiotensin II bei Ratten einen ausgesprochenen diuretischen Effekt zeigt, fehlt diese Wirkung bei demd-Analogon.
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  • 7
    ISSN: 1432-2013
    Keywords: Phosphate influx ; Brush border ; Duodenum ; 1,25-Dihydroxycholecalciferol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Animals treated with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), at doses which decrease the renal production and/or the plasma levels of 1,25-dihydroxycholecalciferol [1,25(OH)2D3], display a reduced net absorption of phosphate. In this study we investigated whether EHDP-treatment and administration of 1,25(OH)2D3 to EHDP-treated animals affected the phosphate influx across the mucosal border of rabbit duodenum. The initial rate of phosphate influx into mucosal cells was measured in isolated intestine. In control, untreated rabbits, the phosphate influx shows a saturable, Na-dependent component and a diffusional, Na-independent uptake. In tissue from rabbits treated for 3 days with EHDP, the phosphate influx was found to be strongly reduced. EHDP-treatment decreased the Na-dependent, carrier mediated phosphate influx in duodenum. Administration of 1,25(OH)2D3 to EHDP-treated animals reversed the reduced phosphate influx. These effects were mainly apparent through changes in theJ mc max of the phosphate influx, which was decreased from 211±38.7 nmole/cm2 h in controls to 42.1±18.1 nmole/cm2 h in the EHDP-treated group and increased to 413±43.6 nmole/cm2 h by 1,25(OH)2D3. The treatment did not appear to affect the diffusional, Na-independent phosphate influx. EHDP-treatment did not affect the influx of alanine in this segment suggesting that EHDP-treatment affects only 1,25(OH)2D3-dependent transport mechanisms. The results suggest that 1,25(OH)2D3 modulates the number of carrier sites available at the mucosal membrane for Na-dependent phosphate entry.
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  • 8
    ISSN: 1432-2013
    Keywords: Natriuretic Hormone ; Third Factor ; Expansion of Extracellular Volume ; Expansion of Plasma Volume ; Isovolemic Cross Circulation ; Natriuretisches Hormon ; Isovolämischer gekreuzter Kreislauf ; Vergrößerung des Extrazellulärvolumens ; Vergrößerung des Intravaskulärvolumens ; Isotonische Salzdiurese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Evidence for the occurrence of a natriuretic factor in rats, in which diuretic and natriuretic responses had been induced, either by expanding the extracellular or the blood volume, was sought in isovolemic cross-circulation experiments, in which a sizable fraction of the cardiac output was exchanged per unit time. In 8 experiments, in which the extracellular space of the donor animal was expanded by infusing isotonic saline, no diuretic or natriuretic response was observed in the recipients, though the recipients' blood underwent the same hemodilution as that of the donors. In six experiments in which the intravascular volume of the donor animal was considerably expanded by injecting heparinized blood obtained from other rats, cross-circulation did not induce any natriuresis or diuresis in the recipients. A natriuretic response was observed in one such cross-circulation experiment and was presumably due to an experimental error. The data do not lend any support to the hypothesis of a circulating natriuretic factor in isotonic saline diuresis or in diuresis after blood volume expansion.
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 132 (1987), S. 517-523 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The influence of the glucocorticoid dexamethasone on the cAMP response to parathyroid hormone (PTH) and various agonists was studied in epithelial monolayers of opossum kidney (OK) cells. The incubation with dexamethasone for 72 hours led to a dose-dependent higher cAMP response to PTH or forskolin in intact cells as well as in digitonin-permeabilized cells. This effect did not appear to result from changes in phosphodiesterase (PDE) activity nor from alterations in cAMP efflux from the cells. Moreover, dexamethasone increased the formation of domes by OK cell epithelium. Thus, dexamethasone seems to promote a more differentiated renal epithelial phenotype as suggested by enhanced hormonal response.
    Additional Material: 4 Ill.
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  • 10
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Parathyroid hormone (PTH) receptors and the biological response to PTH in osteoblasts have been shown to be influenced by glucocorticoids, growth factors, cytokines or PTH itself. Furthermore, components of extracellular matrix (ECM) appear to regulate the response to PTH as well. We investigated the effects of osteoblast-deposited ECM on PTH-related protein (PTHrP)-stimulated cAMP production, PTHrP binding and PTH/PTHrP receptor mRNA in the human osteoblast-like cell line SaOS-2. ECM was laid down by the human osteoblastic cell line MG-63. At confluence, maximal cAMP stimulation induced by 100 nmol/l PTHrP (1-34) was decreased in SaOS-2 cells grown on ECM as compared with cultures on plastic dishes, without any change in PTHrP concentration producing half-maximal stimulation. In contrast, cAMP production stimulated by PGE2 was increased in cells on ECM. Saturable 125I-PTHrP binding (as evaluated by Scatchard plot analysis) was markedly diminished in cells grown on ECM (5,600 ± 2,010 vs. 20,700 ± 1,710 binding sites/cell, × ± S.E.M., P 〈 0.01, n = 4 experiments), without any significant change in affinity (1.3 ± 0.4 vs. 2.5 ± 0.5 nmol/l (NS), in cells on ECM and plastic, respectively). This apparent decrease in membrane receptor density was associated with markedly lower steady state PTH/PTHrP receptor mRNA levels as assessed by Northern blot analysis (ECM/control: 0.4 ± 0.1). A difference in PTH/PTHrP receptor mRNA levels between cells on ECM or on plastic dishes was detectable by 8 hours, but not by 4 hours, after seeding the cells at high density. By 24 hours after plating, PTH/PTHrP receptor mRNA levels were maximally decreased in cells on ECM. These results in the human osteoblast-like cell line SaOS-2 indicate that PTH/PTHrP receptors are down-regulated by growth on ECM. Thus, attachment of bone cells to bone surface could influence differentiation and function of osteoblasts. © 1995 Wiley-Liss Inc.
    Additional Material: 4 Ill.
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