Metabolism of 1-nitropyrene and formation of DNA adducts in Salmonella typhimurium

1-Nitropyrene is slowly reduced by intact cells of Salmonellatyphimurium to yield 1-aminopyrene and N-acetyl-1-aminopyreneplus six unidentified minor products. When the bacteria areexposed to tritiated 1-nitropyrene, increasing amounts of radioactivitybecome bound to DNA as the nitropyrene is metabolized. Enzymatichydrolysis of the labelled DNA yields low molecular weight labelledcompounds which probably represent nucleoside adducts formedby the reaction of nitropyrene metabolites with DNA. Resultswith appropriate mutant strains indicate that bacterial nitroreductasesare involved in activating nitropyrene to a reactive intermediatethat binds to DNA and that nitropyrene adducts in DNA are subjectto excision repair.     

Epidermoid (implantation) cyst after temporomandibular joint surgery.

A case has been reported of an epidermoid inclusion cyst of traumatic origin in the temporomandibular joint region. The cause was attributed to previous surgery.     

Ghrelin alleviates cancer chemotherapy-associated dyspepsia in rodents

Purpose: Chemotherapy treatment may lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Method: We examined the effects of ghrelin in rodent models of CADS induced by treatment with cisplatin. Results: In rats, increased gastric contents and reduced feeding were observed 48 h after injection with cisplatin (6 mg/kg, i.p.). Ghrelin (0.5 mg/kg, i.p.) caused a 16-fold increase in food intake over 1 h in cisplatin/ghrelin-treated rats compared to cisplatin/vehicle-treated rats. A single dose of ghrelin also restored the decreased locomotor activity in rats induced by cisplatin to almost the same level of saline-treated rats. In mice, daily food intake was significantly decreased at 24 h (60%) and 48 h (74%) after cisplatin (20 mg/kg, i.p.). Ghrelin (1 mg/kg, i.p.×2) significantly increased food intake measured at the 48 h time-point in both saline/ghrelin-treated and cisplatin/ghrelin-treated mice, with this effect being most marked in the cisplatin-treated group, where a twofold increase in feeding was observed. In cisplatin-treated mice, delayed gastric emptying was indicated by a 7.7-fold increase in the wet weight of gastric contents and ghrelin improved the gastric emptying index (GEI) by 31% (P<0.01). Conclusion: Together, these results suggest that it is possible to model cancer chemotherapy-induced dyspepsia in rodents and that ghrelin can greatly alleviate the behaviours associated with this syndrome. Agonists at the ghrelin receptor may, therefore, become a useful human therapeutic for this disorder.     

The neurotoxin 2'-NH2-MPTP degenerates serotonin axons and evokes increases in hippocampal BDNF

1-Methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP) causes long-term depletions in cortical and hippocampal serotonin (5-HT) and norepinephrine (NE) that are accompanied by acute elevations in glial fibrillary acidic protein (GFAP) and argyrophilia. To further investigate the hypothesis that these changes are reflective of serotonergic and noradrenergic axonal degeneration, 2'-NH2-MPTP was administered to mice and innervation densities were determined immunocytochemically. Regional responses of the neurotrophin, brain-derived neurotrophic factor (BDNF), to putative damage were also assessed. Three days after 2'-NH2-MPTP, 5-HT axons exhibited a beaded, tortuous appearance indicative of ongoing degeneration. At 21 days, numbers of serotonin axons were significantly decreased, with the greatest axonal losses occurring in cortex and hippocampus. Serotonin axons in the amygdala were contrastingly spared long-term damage, as were 5-HT and NE cell bodies in the brain stem. BDNF protein levels were selectively increased in the hippocampus 3 days post-dose and returned to normal 21 days later. These results, in conjunction with previous findings, demonstrate that 2'-NH2-MPTP causes degeneration of serotonergic axons innervating the cortex and hippocampus on par with depletions in neurotransmitter levels. Moreover, damage to the hippocampus, a brain region important for learning and memory, and the modulation of anxiety and stress responsiveness, results in a transitory increase in BDNF.