G von Boyen

Nerve growth factor secretion in cultured enteric glia cells is modulated by proinflammatory cytokines.

The enteric nervous system is composed of neurones and glial cells. These enteric glia cells (EGC) appear to be essential for the maintenance of gut homeostasis and mucosal integrity. Neurotrophin nerve growth factor (NGF) also plays an important role for the gut integrity by regulating sensory and inflammatory processes in the intestines. Here, we demonstrate EGCs as one source of NGF and show increased levels of NGF mRNA/protein and tropomyosin receptor kinase A (TrkA) mRNA in cultured EGCs upon stimulation with proinflammatory cytokines and lipopolysaccharides. NGF is continuously secreted from cultured EGCs and proinflammatory cytokines and lipopolysaccharides stimulate the secretion of this neurotrophin in a time‐ and dose‐ dependent manner, whereas interleukin‐4 had no effect on NGF expression. Furthermore, NGF secretion was sustained for more than 12 h after withdrawal of the proinflammatory cytokines, suggesting the involvement of transcriptional and/or translational processes. Thus, the release of proinflammatory cytokines can increase NGF secretion by EGCs and leads to a higher expression of TrkA in EGCs. NGF, in turn, can increase visceral sensitivity and, on the other hand, appears to improve gut inflammation. Therefore, NGF secreting EGCs may play a key role in modulating visceral sensitivity and might be involved in inflammatory processes of the gut.

A single dose of intravenous zoledronate prevents glucocorticoid therapy-associated bone loss in acute flare of Crohn's disease, a randomized controlled trial.

OBJECTIVES:To assess the effectiveness and safety of zoledronate (ZOL) in preventing glucocorticoid therapy-associated bone loss in patients with acute flare of Crohns disease (CD) in a randomized, double-blind, placebo-controlled trial.METHODS:Forty CD patients starting a glucocorticoid therapy (60 mg prednisolone per day) for acute flare (CD activity index (CDAI) >220) were randomized to compare the effect of ZOL (4 mg intravenous, n=20) or placebo (n=20) on change in lumbar bone mineral density (BMD). All patients received calcium citrate (800 mg) and colecalciferol (1,000 IU) daily. Dual energy X-ray absorptiometry (DXA) of the lumbar spine (L1–L4) was performed at baseline and day 90. Follow-up examinations at day 1/7/14/30 and 90 included laboratory tests and adverse event/serious adverse events reports.RESULTS:Thirty-six patients were available for per-protocol analysis. With placebo (n=18), a decrease in BMD was seen (T-score: −0.98±0.8, day 0 and −1.25±0.77, day 90, P=0.06), with ZOL (n=18) BMD increased (−1.15±1.02, day 0 and −0.74±1.09, day 90, P=0.03). The change in BMD under placebo (−0.26±0.21) vs. ZOL (+0.41±0.19) was highly significant (P=0.006). In all, 14 out of 18 patients with ZOL had an increase in BMD (+0.64±0.48), 12 of 18 with placebo a decrease (−0.50±0.39). Changes of clinical findings and laboratory results of inflammation (leukocytes, platelets, and C-reactive protein) were the same in- and between-groups throughout the study. With ZOL, serum bone degradation marker β-Cross-Laps decreased. Study medication was safe and well tolerated.CONCLUSIONS:ZOL is effective in preventing glucocorticoid therapy-induced bone loss in patients with acute flare of CD and should be considered whenever a glucocorticoid therapy is started in CD patients.

Acute Pancreatitis in a Patient with Hypercalcemia due to Tertiary Hyperparathyroidism

Hypercalcemia represents an independent risk factor of acute pancreatitis and can result from hyperfunctioning parathyroid glands. Here, we report on a 35-year-old patient who was admitted to our hospital with abdominal pain six weeks after kidney transplantation. Based on laboratory tests and ultrasound imaging, acute pancreatitis with hypercalcemia due to tertiary hyperparathyroidism was diagnosed. Subsequently, the patient was treated by parathyroidectomy with autologous tissue transplantation. This constellation points to acute pancreatitis as a very rare and severe complication of patients developing tertiary hyperparathyroidism-related hypercalcemia from secondary hyperparathyroidism after kidney transplantation.