Secretoneurin is a recently described peptide derived by endoproteolytic processing from secretogranin II, previously named chromogranin C. In this study, we have investigated the distribution of secretoneurin-like immunoreactivity in the human hippocampus in controls and in Alzheimer's disease patients, and compared the staining pattern to that of calretinin. Secretoneurin-like immunoreactivity is present throughout the hippocampal formation. At the border of the dentate molecular layer and the granule cell layer, a band of dense secretoneurin immunostaining appeared. In this part, as in the area of the CA2 sector, the high density of secretoneurin-immunoreactivity coincided with calretinin-like immunoreactivity. The mossy fibre system displayed a moderate density of secretoneurin-immunoreactivity. In the entorhinal cortex, a particularly high density of secretoneurin-immunoreactivity was observed. The density of secretoneurin-like immunoreactivity was significantly reduced in the innermost part of the molecular layer and in the outer molecular layer of the dentate gyrus in Alzheimer's disease. For calretinin-like immunoreactivity, a less pronounced decrease was found in the innermost part of the molecular layer. About 40-60% of neuritic plaques were secretoneurin-immunopositive. This study shows that secretoneurin is distinctly distributed in the human hippocampus and that significant changes of secretoneurin-like immunoreactivity occur in Alzheimer's disease, reflecting synaptic loss.

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Background: Extended hepatectomy is a valid model for the study of acute liver failure. Since the porcine liver is comparable in size, morphology and anatomy to the human liver, we describe a technique employing hepatic ischemia and extended liver resection to induce acute liver failure in a porcine model as a means of studying bioartificial liver support. Method: A subtotal (75–80% resection) extended left hepatectomy was performed in 7 pigs after 60 min warm ischemia of the future remnant liver. After resection, the animals were given the best supportive care and observed until death. Results: All animals died within 18–48 h, none as a result of surgical complications. Gross appearance of the liver showed severe steatosis of the right lateral lobe, and histology revealed severe coagulative necrosis of the whole lobule. Conclusion: This technique of extended liver resection after hepatic ischemia in the porcine model may be useful for studies of potentially reversible acute liver failure and experimental bioartificial support.

The aim of this study was to evaluate the efficacy and safety of our novel Innsbruck Bioartificial Liver (IBAL; US patent no. 10/641275), which contains aggregates of porcine hepatocytes grown under simulated microgravity, in a porcine model of fulminant hepatic failure (FHF). FHF was induced by a combination of 75-80% liver resection and ischemia of the remnant segments for 60 min in 12 pigs. Two experimental groups were studied: the control group (n = 5) received standard intensive care and the study group (n = 5) received IBAL treatment. The survival of pigs with FHF was significantly prolonged by about 150% with IBAL treatment as compared to controls (controls: 20.4 +/- 2.8 h, IBAL: 51.0 +/- 2.2 h; P = 0.00184). In addition, intracranial pressure, blood ammonia, lactate, aspartate aminotransferase, and alkaline phosphatase levels were lower in the IBAL group than in controls, indicating metabolic activity of porcine hepatocytes in the bioreactor. No adverse effects were observed.

Secretoneurin is a 33-amino acid neuropeptide produced by endoproteolytic processing from secretogranin II, which is a member of the chromogranin/ secretogranin family. In this immunocytochemical study we investigated the localization of secretoneurin-like immunoreactivity in the human substantia innominata in relation to the ventral striatopallidal system, the bed nucleus-amygdala complex and the basal nucleus of Meynert. A high density of secretoneurin immunostaining was found in the medial part of the nucleus accumbens. All subdivisions of the bed nucleus of the stria terminalis displayed a very prominent immunostaining for secretoneurin, whereas substance P and enkephalin showed a more restricted distribution. A high concentration of secretoneurin immunoreactivity was also observed in the central and medial amygdaloid nuclei. In the lateral bed nucleus of the stria terminalis and the sublenticular substantia innominata, the appearance of secretoneurin immunoreactivity was very similar to that of enkephalin-like immunoreactivity, exhibiting mostly peridendritic and perisomatic staining. The ventral pallidum and the inner pallidal segment displayed strong secretoneurin immunostaining. Secretoneurin did not label cholinergic neurons in the basal forebrain. This study demonstrates that secretoneurin-like immunoreactivity is prominent in the bed nucleus-amygdala complex, referred to as extended amygdala. The distribution of secretoneurin-like immunoreactivity in comparison with that of other neuroanatomical markers suggests that this forebrain system is a discret compartment in the human forebrain.