Ionamin online research references
Exp Mol Pathol. 1995 Feb;62(1):12-21.
In vivo and in vitro reversibility of chlorphentermine-induced phospholipidosis in rat alveolar macrophages.
McCloud CM, Beard TL, Kacew S, Reasor MJ.
Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, USA.
Chlorphentermine (CP) is a cationic, amphiphilic drug (CAD) that has been studied widely for its ability to induce phospholipidosis, a disorder characterized by excessive accumulation of cellular phospholipid and ultrastructural development of lysosomal lamellar bodies (LLBs) in the cell. The accumulation of inducing drug correlates with increasing phospholipids. In the present study, we examined the reversibility of this disorder in rat alveolar macrophages (AMs) following a 7-day treatment (30 mg/kg/day, ip). The reversibility of phospholipidosis was examined under in vivo conditions and under in vitro conditions in cell cultures for a period of up to 12 days. There was a marked reduction in cellular CP levels and phospholipid content after 4 days of recovery, both in vivo and in vitro; however, there was no indication of significant loss of LLBs. Beyond this time point, ultrastructural recovery from phospholipidosis lagged behind the biochemical recovery temporally and was somewhat less rapid in vitro than in vivo. By 12 days of recovery, AMs from both groups had recovered biochemically, but a moderate level of LLBs was still present in some AMs in the in vitro recovery group. The results of this study indicate that there are more similarities than differences when comparing the recovery of phospholipidotic cells in vitro to that occurring in vivo. We conclude that the use of cell cultures may prove valuable in studying the reversibility of CAD-induced phospholipidosis.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7556587&dopt=Abstract
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Toxicol Appl Pharmacol. 1995 Feb;130(2):316-21.
Biochemical and functional analysis of rat bronchoalveolar macrophages containing chemically induced phospholipid inclusions.
Waites CR, Bugelski PJ, Badger AM.
Department of Toxicology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406.
Cationic amphiphilic drugs (CADs) are structurally characterized by hydrophobic ring structures and hydrophilic side chains. Studies have demonstrated that repeated administration of CADs to experimental animals and humans may induce phospholipid (PL) accumulation within the cells of various tissues. The immunomodulatory azaspiranes are novel CADs with beneficial effects in a number of animal models of autoimmune disease and transplantation. Although the mechanism of action of these compounds is unclear, efficacy in all of the disease models is accompanied by the generation of suppressor cell (SC) activity in various lymphoid organs. SK&F 105685 (N,N-dimethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2-propanamine+ ++ hydrochloride) and two analogs, SK&F 106615 and SK&F 103811, were compared with chlorphentermine and chloroquine for their ability to induce PL accumulation and SC activity. Oral administration of SK&F 105685 and SK&F 106615 caused PL accumulation in bronchoalveolar lavage macrophages (AM) but to a far lesser extent (three- to fivefold) than chlorphentermine. Neither the immunologically unreactive azaspirane SK&F 103811 nor chloroquine affected PL levels. AM from rats treated with SK&F 105685 or SK&F 106615 expressed more potent SC activity than chlorphentermine. Thus, SC activity did not correlate with the extent of PL accumulation. Neither SK&F 103811 nor chloroquine induced SC activity. AM from SK&F 105685-treated rats had an enhanced ability to kill the opportunistic pathogen Candida albicans in vitro indicating that there was no impairment of macrophage-dependent host defense mechanisms.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7871542&dopt=Abstract
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Clin Chem. 1994 Sep;40(9):1703-6.
Microwave-induced rapid preparation of fluoro-derivatives of amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine for GC-MS confirmation assays.
Thompson WC, Dasgupta A.
Department of Pathology, University of New Mexico School of Medicine, Albuquerque 87106.
We prepared trifluoroacetyl, pentafluoropropyl, and heptafluorobutyl derivatives of amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in 45 s, 1 min, and 6 min, respectively, by using microwave irradiation. Conventional techniques require heating the reaction mixture for 15 min at 40 degrees C for trifluoroacetyl derivatives, 15 min at 75 degrees C for pentafluoropropyl derivatives, and 40 min at 60 degrees C for heptafluorobutyl derivatives. The mass-spectral fragmentation patterns and the gas-chromatographic retention times of the derivatives obtained by both microwave irradiation and conventional heating were similar. Perfluorooctanoyl derivatives of amphetamine can be prepared quantitatively by either heating the reaction mixture for 30 min at 60 degrees C or by 1 min of microwave irradiation. Conversion of methamphetamine and MDMA to the corresponding perfluorooctanoyl derivatives was not quantitative by either technique, although the yield of the derivative in the conventional technique was much higher.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7915216&dopt=Abstract
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