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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 65 (1991), S. 537-541 
    ISSN: 1432-0738
    Keywords: Sodium dichromate ; Nephrotoxicity ; Hepatotoxicity ; Lipid peroxidation ; Phenobarbital
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A comparison of the effects of intraperitoneal and subcutaneous routes of administration of sodium dichromate on nephrotoxicity in rats was studied. Dichromate when injected subcutaneously (SC group) produced a higher degree of nephrotoxicity than when administered intraperitoneally (IP group). It caused severe progressive proteinuria followed by polyuria and glucosuria, reaching maximum levels at 3 days after treatment in the SC group, whereas it produced mild proteinuria without glucosuria in the IP group. The dose-dependent increases in blood urea nitrogen (BUN) and creatinine concentrations, shown in the SC group, were not observed in the IP group. However, between the two groups, there were no great differences in either the urinary excretion rate of chromium or the electrophoretic patterns of urinary protein in the day 1 urine specimens. Pretreatment of phenobarbital (PB) had no remarkable effect on the dichromate-induced nephrotoxicity. In contrast, it potentiated dichromate-induced hepatotoxicity, the indices of which were the elevation in serum alanine aminotransferase (ALT) activity and hepatic lipid peroxide formation. These results suggest that the dependence of dichromate-induced nephrotoxicity on the route of administration is related to the chemical forms of chromium reaching the kidney, and the necrotizing property of dichromate results from its metabolic fate in vivo.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 66 (1992), S. 646-651 
    ISSN: 1432-0738
    Keywords: Sodium dichromate ; Nephrotoxicity ; Glutathione ; Ascorbate ; Carbohydrate metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ascorbate treatment 30 min prior to sodium dichromate (20 or 30 mg/kg, s.c.) shows higher potency than that of glutathione (GSH) in protecting against both the metabolic disturbance and nephrotoxicity induced by dichromate. However, ascorbate treatment after 2 h of dichromate intoxication had no effect on dichromate-induced blood urea nitrogen (BUN) elevation 3 days after intoxication. In contrast, dichromate-induced glucosuria, which reached maximum levels at 3 days after treatment, was significantly decreased by GSH or N-acetyl cysteine (NAC) treatment, even if its administration was after 24 h of dichromate intoxication. Pretreatment with GSH depletors such as diethyl maleate (DEM) and buthionine sulfoximine (BSO) had no effect on dichromate-induced nephrotoxicity. GSH levels in the liver and kidney were not affected at 3 h after dichromate treatment. However, dichromate significantly increased tissue GSH levels with a marked increase in liver per kidney GSH ratio at 24 h after treatment, if food was withheld subsequent to dichromate treatment, indicating that GSH biosynthesis resulted from the accelerated protein breakdown. These results suggest that GSH-mediated dichromate reduction is not a kinetically favorable pathway in vivo; however, GSH plays an important role in protection against dichromate-induced nephrotoxicity. In addition, the cellular metabolism of dichromate in the early period after treatment is important in the pathogenesis of its nephrotoxicity.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-904X
    Keywords: nonionic surfactants ; cloud point ; cloud point boosters ; poloxamers ; poloxamines ; liquid formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the cloud point of a variety of nonionic surfactants and to search for means to raise the surfactant cloud point in liquid formulations. Methods. Cloud points of nonionic surfactants were determined visually in a water bath. Organic compounds, many of which have been used as pharmaceutical excipients, were tested initially for effect on the cloud point of poloxamine 908. Four effective cloud point boosters (CPBs) from different structural classes were further tested on additional surfactants. Results. A number of compounds can raise the cloud point of nonionic surfactants. These cloud point boosters are classified into two categories: nonionic and ionic. The nonionic CPBs include poly(ethylene glycols), propylene glycol, methanol, ethanol, isopropanol, and 2-hydroxypropyl-β-cyclodextrin. They are effective at molar concentrations. The ionic CPBs include anionic and cationic surfactants, charged phospholipids, long chain fatty acids, and bile salts. They are effective at millimolar concentrations. Conclusions. The cloud point of nonionic surfactants used in liquid formulations can be modulated through the proper choice of excipient.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-904X
    Keywords: nanocrystals ; submicron crystals ; suspensions ; steam sterilization ; physical stability ; surfactants ; cloud point ; ethyl diatrizoate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study the effects of formulation variables on the physical stability of a submicron crystal (nanocrystal) suspension under steam sterilization conditions. Methods. Suspensions of ethyl diatrizoate nanocrystals were prepared by wet milling in the presence of the surfactant poloxamine 908. Particle size distribution and zeta potential were measured by photon correlation spectroscopy. Results. On heating, the mean particle size of the nanocrystal suspension remained essentially unchanged up to 110°C, the cloud point of the stabilizing surfactant, but increased significantly above that temperature. The increase in particle size was a result of particle aggregation rather than crystal growth. Adding a cloud point booster to the suspension significantly minimized the particle aggregation at high temperatures. The purity of poloxamine 908 and the tonicity agent and buffer salt used also affected the heat stability of the suspension, the latter agents apparently through altering the surfactant cloud point. Conclusions. The aggregation of the ethyl diatrizoate nanocrystalline suspension under steam sterilization conditions was a result of phase separation of the stabilizing surfactant at its cloud point. When formulated with a cloud point booster to prevent the phase-separation, the suspension maintained its physical stability under steam sterilization without any significant change in particle size distribution.
    Type of Medium: Electronic Resource
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