STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS : III. ANAPHYLAXIS INDUCED BY ARSPHENAMINE

Experiments are described which show that with a given treatment guinea pigs can be sensitized to arsphenamine, so that a considerable percentage die in anaphylactic shock on intravenous administration of the substance.     

Wachstumshormone und BMP

BMP (bone morphogenetic proteins) belong to the TGFβ superfamily and appear to play a central role in fracture healing. Two growth factors have been in use since 2001 as an approved therapy option for the delayed healing of fractures or open lower leg fractures: BMP-7 for delayed fracture healing and BMP-2 for open lower leg fractures. The aim of the present study was to examine the effectiveness of the BMP in fracture healing and compare fracture healing without the use of bone growth factors. Patients who were treated with BMP-7 following repeated attempts to treat atrophic pseudoarthrosis of the tibia were compared with a large standardized collective of patients with first-time spongiosa plastic. Patients receiving BMP-7 showed significantly better bone fusion in the fracture area at radiological examination at four months. In order to prove the advantages of this procedure, as well as to be able to recommend it as a treatment modality, further studies on larger patient collectives and prospective control groups are needed.     

Receptor-mediated ingestion responses by lung macrophages from a canine model of ARDS

Receptor-mediated ingestion was examined in macrophages derived from a canine model of the adult respiratory distress syndrome (ARDS). The results showed that Fc-mediated ingestion by alveolar macrophages (AM) and macrophages from lung parenchyma (PM) was significantly diminished when compared with their respective controls. Pulsing all the experimental groups with lipopolysaccharide (LPS) for 1 hr in vitro failed to either enhance the response or return the activity to levels achieved by control cells. In parallel studies, an analysis of C3b-mediated ingestion showed that both the experimental AM and PM performed this function only at a magnitude equal to the control cells. Similar responses were observed when an LPS pulse was performed. Although there was a reduction in Fc-mediated ingestion and an apparent restraint of the C3b-mediated ingestion, both AM and PM expressed a significantly enhanced ability to spread. These results suggested that the canine model of ARDS alters at least one select macrophage function that may be important to subsequently protect the host. Such disturbances in the cellular immune response may contribute to the progression of infection and lung pathology associated with this disease process.     

Effects of glutamine-enriched parenteral nutrition on the exocrine pancreas

Total parenteral nutrition (TPN) is associated with intestinal and pancreatic atrophy and pancreatic exocrine insufficiency. Recent investigations have demonstrated that the addition of glutamine to intravenous feedings attenuates TPN-associated intestinal atrophy. However, the effect of glutamine-supplemented intravenous feedings on the pancreas of intact animals is unknown. This study compared the effects of an intravenous infusion of a 2% glutamine-enriched diet (GLN) with an isonitrogenous, isocaloric diet without glutamine (CONT) on the composition and structure of the exocrine pancreas in laboratory rats with and without a 60% small bowel resection. In nonresected, TPN-fed animals, pancreatic weight was significantly increased in the GLN group when compared to CONT (645 +/- 33 g vs 554 +/- 20 g, p less than 0.05). Nonresected GLN animals also had increased pancreatic DNA (3.82 +/- 0.19 mg vs 2.91 +/- 0.49 mg, p less than 0.005) and protein contents (93.0 +/- 5.9 mg vs 76.6 +/- 7.0 mg, p = 0.08) compared to control. Similar significant increases in pancreatic weight, DNA, and protein were observed in intestinally resected animals fed the glutamine diet. When data from CONT and GLN animals were pooled and analyzed together, glutamine significantly increased total pancreatic trypsinogen and lipase contents (p less than 0.05). The increase in trypsinogen in resected GLN animals was significantly greater than in CONT animals (283 +/- 22 vs 139 +/- 23, p less than 0.005). Biochemical and morphometric observations demonstrated that the trophic effects of glutamine on the exocrine pancreas were manifest by acinar hyperplasia and not hypertrophy. Glutamine appears to be an important nutrient for pancreatic exocrine tissue during TPN.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppression of hippocampal cell proliferation by short-term stimulant drug administration in adult rats

Sleep loss is known to potently suppress adult hippocampal cell proliferation and neurogenesis. Whether sleep suppression following acute administration of stimulant drugs also decreases hippocampal cell proliferation is not known. The present study examined the effect of three mechanistically distinct stimulants (caffeine, methamphetamine and modafinil) on cell proliferation. To maximize sleep suppression, these drugs were administered to rats (three i.p. injections, once every 4 h) during their sleep period (i.e. 12-h light phase). At the end of the light phase, 5-bromo-2'-deoxyuridine (200 mg/kg, i.p.) was injected and animals were killed 2 h later. Polygraphic recordings and locomotor activity measurements confirmed the wake-promoting and sleep-suppressing actions of each treatment. Results indicate that caffeine (20 mg/kg), methamphetamine (1.5 mg/kg) and modafinil (300 mg/kg) differentially suppressed sleep (45–91%) and selectively reduced cell proliferation in the hilus (12–44%), these results being significant for both caffeine and modafinil. When the same experiment was repeated in the dark (active) phase, the suppressant effect on hippocampal cell proliferation was either absent or greatly attenuated. In a further experiment, the effect of acute modafinil treatment in the light phase was shown to persist for 3 weeks after BrdU administration. We hypothesize that the differential effect of the stimulant drugs in the light vs. dark phase is attributable primarily to sleep suppression in the light. As abuse of stimulant drugs invariably leads to disrupted sleep in humans, our results suggest that they may, at least in part, decrease hippocampal neurogenesis via sleep loss and thereby adversely affect hippocampal-dependent processes.