About: Meth- is a research topic. Over the lifetime, 3145 publications have been published within this topic receiving 70582 citations.
Papers published on a yearly basis
TL;DR: The accumulated evidence indicates that multiple events converge to mediate METH-induced terminal degeneration and neuronal apoptosis, and suggest that pharmacological strategies geared towards the prevention and treatment of the deleterious effects of this drug will need to attack the various pathways that form the substrates of METH toxicity.
Abstract: Methamphetamine (METH) is an illicit psychostimulant that is widely abused in the world. Several lines of evidence suggest that chronic METH abuse leads to neurodegenerative changes in the human brain. These include damage to dopamine and serotonin axons, loss of gray matter accompanied by hypertrophy of the white matter and microgliosis in different brain areas. In the present review, we summarize data on the animal models of METH neurotoxicity which include degeneration of monoaminergic terminals and neuronal apoptosis. In addition, we discuss molecular and cellular bases of METH-induced neuropathologies. The accumulated evidence indicates that multiple events, including oxidative stress, excitotoxicity, hyperthermia, neuroinflammatory responses, mitochondrial dysfunction, and endoplasmic reticulum stress converge to mediate METH-induced terminal degeneration and neuronal apoptosis. When taken together, these findings suggest that pharmacological strategies geared towards the prevention and treatment of the deleterious effects of this drug will need to attack the various pathways that form the substrates of METH toxicity.
TL;DR: It is suggested that the poor immunogenicity of hsp90 results from its lack of a measurable ATPase activity, which has been implicated in the ability of HSPs to transfer peptide to acceptor molecules.
Abstract: Stress-induced proteins (or heat shock proteins (HSPs)) of 96 kDa size (gp96) have been shown previously to elicit specific immunity to tumors from which they are isolated. In this report, we show that in contrast to Meth A-derived gp96, gp96 preparations derived from normal tissues did not elicit immunity to Meth A sarcoma at any dose tested. Further, in light of recent studies showing that other major cellular HSPs hsp90 and hsp70 also elicit tumor-specific immunity, we have compared the relative immunogenicities of gp96, hsp90, and hsp70 derived from the Meth A sarcoma. The proteins gp96 and hsp70 were observed to be highly and equally immunogenic, whereas the immunogenicity of hsp90 was approximately 10% of that of gp96 or hsp70. It is suggested that the poor immunogenicity of hsp90 results from its lack of a measurable ATPase activity, which has been implicated in the ability of HSPs to transfer peptide to acceptor molecules. This is the first study that documents the lack of immunogenicity of gp96 preparations derived from normal tissues and compares the immunogenicity of each of the three major cellular HSPs in one tumor system.
TL;DR: Agents which prevent the METH-induced decrease of neostriatal tyrosine hydroxylase activity, i.e., haloperidol, alpha-methyl-p-tyrosine and gamma-aminobutyric acid transaminase inhibitors also prevented the decrease in TPH activity caused by METH.
Abstract: Tryptophan hydroxylase (TPH) activity was measured in various rat brain regions after administering large doses of methamphetamine (METH). After four sequential doses of METH (15 mg/kg), given every 6 hr, TPH activity was decreased (to approximately 10% of control) in both the neostriatum and hippocampus. The depression of enzyme activity persisted for at least 30 days. When compared with the depression of neostriatal tyrosine hydroxylase activity, the depression of neostriatal and hippocampal TPH activity occurred sooner and was more pronounced. The depression of TPH activity was dependent on the number of doses and the amount of drug administered. Five days after one to two doses of METH, a transient recovery was observed but when four doses were given, the enzyme was depressed. No decrease in TPH activity was observed in brain areas containing serotonergic cell bodies. Agents which prevent the METH-induced decrease of neostriatal tyrosine hydroxylase activity, i.e., haloperidol, alpha-methyl-p-tyrosine and gamma-aminobutyric acid transaminase inhibitors also prevented the decrease in TPH activity caused by METH. In addition, fluoxetine, an inhibitor of 5-hydroxytryptamine re-uptake, prevented the METH-induced decrease in neostriatal and hippocampal TPH activity but did not alter the decrease in nenostriatal tyrosine hydroxylase activity.
TL;DR: It was concluded that short- and long-term decreases in striatal DA levels depend on the degree of hyperthermia produced during METH exposure but cannot be produced byhyperthermia alone.
Abstract: The depletion of striatal dopamine (DA) that can occur after methamphetamine (METH) administration has been linked to METH-induced hyperthermia. The relationship between METH-induced hyperthermia, neurotoxicity (striatal DA depletions) and compounds that protect against METH neurotoxicity was further investigated in this study. Typically, rats exposed to METH die when their body temperatures exceed 41.3 degrees C but such hyperthermic rats can be saved by hypothermic intervention. Subsequently, rats saved by hypothermic intervention have greater depletion of striatal DA at an earlier time of onset (18 hr or less post-METH) than do METH-exposed rats that do not attain such high temperatures. Striatal damage was present 3 days post-METH in these hyperthermic rats, as assessed by silver degeneration of terminals and increases in the astrocytes that express glial fibrillary acidic protein immunoreactivity. By contrast, alterations in the number of [3H]dizoclipine (MK-801) binding sites in cortical or striatal membranes at 1, 3 or 14 days post-METH were not detected. The experiments showed that mean and maximal body temperature correlated well with striatal DA concentrations 3 days post-METH (r = -0.77, n = 58), which suggests a role for hyperthermia in METH neurotoxicity. However, hyperthermia (alone or with haloperidol present) induced by high ambient temperatures did not deplete striatal DA in the absence of METH. Haloperidol, diazepam and MK-801 all reduced METH-induced striatal DA depletion to a degree predicted by their inhibition of hyperthermia and increased ambient temperature abolished their neuroprotection. Although an interleukin-1 receptor antagonist reduced maximal body temperature enough to lower the lethality rate, it did not reduce the temperature sufficiently to block METH neurotoxicity. It was concluded that short- and long-term decreases in striatal DA levels depend on the degree of hyperthermia produced during METH exposure but cannot be produced by hyperthermia alone. In addition, several agents that block DA depletions do so by inhibiting METH-induced hyperthermia. Finally, the results suggested a role for interleukin-1 in the extreme hyperthermia and lethality produced by METH.
TL;DR: The data suggest that therapeutic doses of glucocorticoids induce obesity mostly by increasing energy intake, an effect which may be related to the ability of gluc Cocorticoid to act directly or indirectly on the central regulation of appetite.
Abstract: The effect of glucocorticoid administration on energy metabolism and food intake was studied in 20 healthy, nondiabetic Caucasian male volunteers [27 +/- 5 (SD) yr, 72 +/- 9 kg, 20 +/- 7% body fat] randomly and blindly assigned to glucocorticoid (methylprednisolone, METH; n = 10) or placebo (PLAC; n = 10) treatment. Each subject was studied twice: during a weight maintenance diet and during ad libitum food intake. Energy metabolism was measured by indirect calorimetry and food intake by an automated food-selection system. Twenty-four-hour urinary norepinephrine excretion (24-h NE) was used as an estimate of sympathetic nervous system activity. During weight maintenance, METH intravenous infusion (125 mg/30 min) increased energy expenditure compared with PLAC, and after 4 days of oral therapy, METH (40 mg/day) decreased 24-h NE and increased energy expenditure compared with PLAC. During ad libitum food intake, after 4 days of METH (40 mg/day) or PLAC oral therapy, both groups increased their energy intake over weight maintenance, but the increase was significantly larger in the METH group compared with the PLAC group (4,554 +/- 1,857 vs. 2,867 +/- 846 kcal/day; P = 0.04). Our data suggest that therapeutic doses of glucocorticoids induce obesity mostly by increasing energy intake, an effect which may be related to the ability of glucocorticoids to act directly or indirectly on the central regulation of appetite.