Plurihormonal Pit-1 lineage adenoma presenting as meningitis with recurrence after somatostatin analogue.

A 21 year-old woman was found to have a pituitary macroadenoma following an episode of haemophilus meningitis. Biochemical TSH and GH excess was noted, although with no clear clinical correlates. She was treated with a somatostatin analogue (SSA), which restored the euthyroid state and controlled GH hypersecretion, but she re-presented with a further episode of cerebrospinal fluid (CSF) leak and recurrent meningitis. Histology following transsphenoidal adenomectomy revealed a Pit-1 lineage plurihormonal adenoma expressing GH, TSH and PRL. Such plurihormonal pituitary tumours are uncommon and even more unusual to present with spontaneous bacterial meningitis. The second episode of CSF leak and meningitis appears to have been due to SSA therapy-induced tumour shrinkage, which is not a well-described phenomenon in the literature for this type of tumour. Learning points: Pit-1 lineage GH/TSH/PRL-expressing plurihormonal pituitary adenomas are uncommon. Moreover, this case is unique as the patient first presented with bacterial meningitis. Inmunohistochemical plurihormonality of pituitary adenomas does not necessarily correlate with biochemical and clinical features of hormonal hypersecretion. Given that plurihormonal Pit-1 lineage adenomas may behave more aggressively than classical pituitary adenomas, accurate pathological characterization of these tumours has an increasing prognostic relevance. Although unusual, a CSF leak and meningitis may be precipitated by SSA therapy of a pituitary macroadenoma via tumour shrinkage.

The differential tissue expression of inflammatory, oxidative stress, and apoptosis markers in human uncontrolled non-heart-beating donors.

BACKGROUND: Uncontrolled non-heart-beating donor (UNHBD) transplantation offers a major opportunity to ameliorate the effects of the donor shortage. However, little is known about the true status of the organs obtained from these donors. UNHBD transplantation is performed under unfavorable conditions and involves exposure to several harmful stimuli that have been identified as triggers for immediate inflammatory response, oxidative stress, and apoptotic phenomena. This adverse scenario could explain the higher rates of graft dysfunction due to primary nonfunction traditionally observed in NHBD. Our aim was to assess the expression of proinflammatory, oxidative, and apoptotic markers in liver, lung, and pancreas tissue samples obtained from UNHBD and to compare these expression levels with those observed in brain-dead donors (BDD). METHODS: Samples from human type 2 NHBD and BDD were obtained at the end of cold storage. Interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-10, endothelial nitric oxide synthase, inducible nitric oxide synthase, type 1 heme oxygenase, type 2 heme oxygenase, Bax, and Bcl-2 protein and mRNA expression, as well as catalase, glutathione peroxidase, and glutathione reductase tissue activity, were determined. RESULTS: UNHBD showed similar or lower expression of proinflammatory mediators and apoptosis markers in all three organs without modifications to the anti-inflammatory cytokines. Although the major oxidative stress marker levels were also comparable in both types of donors, the type 1 heme oxygenase mRNA expression and antioxidant enzyme activity were slightly diminished in UNHBD. CONCLUSIONS: The initial tissue damage generated during the UNHB donation process is at least comparable with that observed in BDD. However, although the expression of the immediate immune response and apoptosis markers is similar, a mild impairment of the local antioxidant activity was observed.

Tacrolimus modulates liver and pancreas nitric oxide synthetase and heme-oxygenase isoforms and cytokine production after endotoxemia.

Cytoprotective effects of tacrolimus are due to its unspecific anti-inflammatory and anti-oxidant properties. Neither the exact mechanisms nor if there is any organ-specificity or dose-dependent response have not been yet elucidated. Our aim was to evaluate the effect of tacrolimus on oxidative stress and mediator production in liver and pancreatic tissue secondary to endotoxemia. Wistar rats were pretreated with intraperitoneal injection of tacrolimus (0.07, 0.15, and 0.3mg/kg) 24h before Escherichia coli LPS was administrated. Animals were sacrificed 24h after LPS administration and iNOS, eNOS, and nNOS and type 1 and 2 heme-oxygenase (HO) expression were measured. TNF-α and IL-1 tissue expression and plasmatic NO, CO, TNF-α, and IL-1 were also determined. LPS exposure increased iNOS expression in both organs, eNOS did not show variations and liver nNOS expression was significantly lower. Tacrolimus diminished both pancreas and liver iNOS and nNOS expression. Both liver and pancreatic eNOS expression augmented when tacrolimus was administrated. High doses of tacrolimus were correlated with ameliorated liver HO-1 plus HO-2 and pancreas HO-1 expression after LPS stimulation. Tacrolimus treatment diminished TNF-α but not IL-1 expression increase after LPS challenge in hepatic tissue. Pancreatic TNF-α and IL-1 values diminished partially when high doses were employed. Plasmatic NO, CO, TNF-α, and IL-1 concentrations increase after LPS challenge was diminished when highest doses of tacrolimus were given. In conclusion, tacrolimus exerts a protective effect on commonly observed harmful phenomena after LPS stimulation by modulating liver and pancreas oxidative enzyme expression and cytokine production.