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Fly artifacts (FA) are bloodstains resulting from insect activity at a crime scene, usually by feeding on human blood. Whether these artifactual stains might be useful for forensic toxicological investigations in cases of absence of conventional and unconventional matrices, for example, in cases concealment of the body or of extensive putrefaction, has not yet been investigated. The purpose of this study is to understand if FA trace evidence permits toxicological analysis when traditional matrices are not available. To this aim, FA experimentally produced by Calliphora vomitoria feeding on human blood of a cocaine and heroin user were collected from absorptive and non-absorptive material. FA material was analyzed by a new simple and fast LC-MS/MS method. Results were evaluated in terms of presence of the drug and relative amount of the detected molecules. From a qualitative point of view, the analysis of FA revealed all the substances originally detected in post-mortem blood in both cases. The ratios of cocaine/benzoylecgonine, codeine/morphine, and 6-monoacetylmorphine/morphine recovered in FA from cotton-textile materials and from non-absorptive surfaces were consistent with data resulted from original post-mortem blood. The preliminary study herein reported demonstrated that FA are extremely informative in case of cocaine and heroin users and merit further research in order to be applied in real caseworks.

It is now widely recognized that nonsteroidal anti-inflammatory drugs (NSAIDs) may cause extensive damage to the intestine. The pathogenesis of NSAID-induced intestinal injury, however, is still controversial and both local irritant actions and cyclooxygenase (COX) inhibition have been proposed as underlying mechanisms. In this study we investigated further on NSAID-induced intestinal damage by using nonselective (indomethacin and ibuprofen), COX-1 selective (SC-560) or COX-2 selective (celecoxib) inhibitors. NSAIDs were administered orally to conscious rats and small intestinal injury was evaluated 24 h afterwards in terms of macroscopic and microscopic alterations, myeloperoxidase activity, lipid peroxidation, number of enterobacteria in the mucosa and epithelial mucin content. Oral administration of indomethacin (20 mg/kg) induced macroscopic and microscopic damage to the small intestine, increased translocation of enterobacteria from lumen into the mucosa, myeloperoxidase activity and lipid peroxidation. Ibuprofen (120 mg/kg), SC-560 (20 mg/kg), celecoxib (60 mg/kg) or the combination of SC-560 plus celecoxib did not cause any intestinal injury nor modified the number of bacteria in mucosal homogenates. SC-560 significantly increased both myeloperoxidase activity and lipid peroxidation, whereas celecoxib significantly reduced myeloperoxidase levels, while leaving unaltered lipid peroxidation. Finally, all NSAIDs, mostly indomethacin, increased neutral mucins and decreased acidic mucins in the intestinal goblet cells. These results indicate that inhibition of cyclooxygenase, although variably influencing mucosal integrity homeostasis, is not sufficient to initiate acute intestinal damage in rats. Moreover, topical mucosal injury induced by the NSAID molecule seems to be a critical factor in the development of intestinal injury.

The discovery of a second isoform of cyclooxygenase has led to a re-evaluation of the mechanisms underlying the adverse effects of nonsteroidal anti-inflammatory drugs, focusing in particular on the gastrointestinal system. We investigated the involvement of cyclooxygenase-1 and -2 in the regulation of gastric acid secretion and cardiovascular functions in anesthetized rats, after acute intravenous administration of the selective cyclooxygenase-1 inhibitor SC-560, the selective cyclooxygenase-2 inhibitor celecoxib and the nonselective inhibitor indomethacin. Indomethacin, celecoxib and SC-560 did not significantly modify basal acid secretion. Indomethacin and celecoxib were also ineffective on the acid secretion stimulated by pentagastrin; by contrast, SC-560 significantly enhanced the acid secretion stimulated by pentagastrin, electrical vagal stimulation or histamine. The stimulatory effects of SC-560 were prevented by cervical vagotomy, atropine and famotidine. Indomethacin caused either no change, increasing or decreasing effects on mean arterial pressure and heart rate. By contrast, SC-560 was unable to change cardiovascular parameters at 5 mg/kg, while inducing a marked bradycardia at 10 mg/kg. Celecoxib was ineffective. Our findings indicate that cyclooxygenase-1-derived prostaglandins are involved in the regulation of stimulated acid secretion and of basal heart rate; the role of prostaglandins in the acute control of systemic blood pressure under resting conditions seems to be negligible.

The effects of the cannabinoid (CB)-receptor agonists WIN55,212-2 and HU-210 and the selective CB(1)-receptor antagonist SR141716A were tested on in vitro and in vivo acid secretion assays from the rat. In the isolated gastric fundus from immature rats, WIN55,212-2 (0.001-30 microM), HU-210 (0.001-10 microM), or SR141716A (0.1-10 microM) did not change the basal acid output or acid responses to histamine, pentagastrin, or electrical field stimulation. HU-210 (0.3 micromol/kg, intravenously) inhibited the acid response to pentagastrin in anesthetized adult, young, or immature rats with lumen-perfused stomachs; moreover, HU-210 reduced vagally induced acid secretion in adult animals, its antisecretory effect being reversed by SR141716A (0.65 micromol/kg, intravenously). In vitro and in vivo data indicate that CB(1) receptors are not located on parietal cells but, rather, on vagal pathways (possibly at preganglionic sites) supplying the gastric mucosa. The lack of effect of CB-receptor ligands in vitro cannot be ascribed to the use of immature rats, since HU-210 inhibited stimulated acid secretion in vivo, irrespective of the animal age.

Bacterial antigens, such as intestinal microflora, are known to play a role in the pathogenesis of human inflammatory bowel disease (IBD). Tylosin, a macrolide antimicrobial agent, has proven to be effective in cat and dog chronic colitis, but the reasons underlying this efficacy are still unclear. In the present study we evaluated the effects of tylosin on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in the rat, in comparison with the antibacterial drug metronidazole and the corticosteroid budesonide. Colitis was induced by a single intrarectal administration of 10 mg TNBS under light ether anesthesia. Tylosin (20 mg/kg twice a day), metronidazole (160 mg/kg twice a day) and budesonide (500 µg/kg once a day) were given orally for up to 6 days to separate groups of rats. The animals were sacrificed after 6 days and colonic lesions evaluated (colon weight, macroscopic and histologic damage, myeloperoxidase activity). Tylosin and metronidazole significantly lowered macroscopic lesion score, reduced colon weight, the severity of histologic lesions and myeloperoxidase activity; budesonide did not significantly change the parameters of colonic inflammation. These data indicate a protective effect of tylosin against intestinal inflammation, suggesting a major role for bacteria, anaerobes in particular, in the development of TNBS-induced mucosal damage.