Perinatal hypoxia/ischemia (HI) is a common cause of neurological deficits in children. Interleukin-1 (IL-1) activity has been implicated in HI-induced brain damage. However, the mechanisms underlying its action in HI have not been characterized. We used a 7-day-old rat model to elucidate the role of nuclear factor-jB (NF-jB) activation in HI stimulation of IL-1 signaling. HI was induced by permanent ligation of the left carotid artery followed by 90 min of hypoxia (7.8% O 2 ). Using ELISA assays, we observed increased cell death and caspase 3 activity in hippocampus and cortex 3, 6, 12, 24 and 48 h post-HI. IL-1b protein expression increased, beginning at 3 h after HI and lasting until 24 h post-HI in hippocampus and 12 h post-HI in cortex. Intracerebroventricular injection of 2lg IL-1 receptor antagonist (IL-1Ra) 2 h after HI significantly reduced cell death and caspase 3 activity. Electrophoretic mobility shift assay analyses of hippocampus and cortex after HI for NF-jB activity showed increased p65/p50 DNA-binding activity at 24 h post-HI. Western blot analyses showed significant nuclear translocation of p65. Protein expression levels of two known inflammatory agents, inducible nitric oxide synthase and cycloxygenase 2, known to be transcriptionally regulated by NF-jB, also increased at 24 h after HI. All these HI-induced changes were reversed by IL-1Ra blockade of IL-1 signaling, consistent with IL-1 triggering of inflammatory apoptotic outcomes via NF-jB transcriptional activation. The observed increase in cytoplasmic phosphorylated inhibitor jBa (IjBa) and nuclear translocation of Bcl-3 24 h after HI was also significantly attenuated by IL-1Ra blockade, suggesting that HI-induced IL-1 activation of NF-jB is via both the degradation of IjBa and the nuclear translocation of Bcl-3. Keywords: Bcl-3, hypoxia/ischemia, inhibitor jBa, interleukin-1, nuclear factor-jB. Perinatal hypoxia/ischemia (HI) during gestation/delivery or the accidental asphyxia of infants is a common cause of neurological deficits and delayed cognitive and behavioral deficits (Kaltschmidt et al. 1994). A rapidly expanding body of evidence indicates that inflammatory mediators, including inflammatory cytokines, contribute substantially to the pathogenesis associated with perinatal HI brain injury (Hagberg et al. 1996;Bona et al. 1999;Hedtjarn et al. 2002). The best-characterized early response inflammatory cytokine is interleukin-1 (IL-1) (Szaflarski et al. 1995). The IL-1 family includes the agonists IL-1a and IL-1b, the endogenous receptor antagonist IL-1 receptor antagonist (IL-1Ra), and a newly discovered member, IL-18/IL-1c (Shapiro et al. 1998). IL-1b has consistently been detected in central nervous system after injury to the brain or spinal cord (Rothwell et al. 1997;Nesic et al. 2001). There is also evidence showing a correlation between increased IL-1b levels and subsequent neurodegeneration. Thus, administration of exogenous IL-1b markedly exacerbates neuronal/glial damage in rodents exposed to focal cerebral ischemia or...

The kinetics of tryptic breakdown of the heavy chain of chymotryptic myosin subfragment 1 (Sl) according to the following scheme (where the numbers respresent approximate masses in kDa) are altered at 21 "C by divalent process affects the tryptic fragmentation of S1 similarly to, but less effectively than, nucleotides. Acts-S1 formation prevents the effect of ATP on fragmentation. At 37 'C S1 loses ATPase activity; tryptic digestion proceeds more rapidly and the 50-kDa and 25-kDa fragments are degraded to small peptides. Nucleotides protect against the effects of higher temperature by producing conformational changes not only in the 27-kDa N-terminal portion (containing the putative nucleotide binding site) of the heavy chain of S1 but also in the 50-kDa peptide.Previous studies have shown that, on further digestion with trypsin, the heavy chain of chymotryptic myosin subfragment 1 (Sl) is split into two fragments with approximate masses of 75 kDa and 20kDa; the latter contains the two reactive thiols, SH-1 and SH-2 [I]. The 75-kDa fragment is further degraded into an N-terminal 25-kDa fragment and an adjacent 50-kDa polypeptide with the transient appearance of a 27-kDa fragment [I -31. It has been suggested that the 25-kDa fragment, which was found to be the binding site of a photoaffinity ATP analog [4], is formed by two parallel routes directly from the 75-kDa fragment and indirectly with the 27-kDa fragment as precursor [ 5 ] .Alterations in the proteolytic fragmentation pattern induced by actin, nucleotide or metal binding indicate that structural changes take place in the myosin head region upon their interactions. Thus actin inhibits the proteolytic cleavage of the S1 heavy chain at the junction between the 50-kDa and 20-kDa fragments. The cleavage abolishes the A preliminary report has been presented [(1982) Biophys. J . 37, 38al.Abbreviations. AdoPP[NH]P, adenosine 5'-[P,y-imido]triphosphate; HMM, heavy meromyosin; S1, myosin subfragment 1 ; Nbs,, 5,5'-dithiobis(2-nitrobenzoic acid) ; NaDodSO,, sodium dodcecyl sulfate.

In the present article, the authors want to present the results of a retrospectively evaluated consecutive series of patients with surgically treated isolated orbital floor fractures (OFF; "blow-out fractures") concerning the functional outcome after OFF and give detailed recommendations based on the clinical and radiological findings. A series of 60 patients with isolated OFF over a 5-year period needing surgically repair at the same institution were evaluated. Patient data were analysed in terms of preoperative and postoperative clinical parameters and radiological findings. The analysed parameters were type of fracture, diplopia, gaze restriction, enophthalmos, materials used for repair, surgical approach and timing of the surgical intervention. Burst type fractures were more often found than punched-out fractures. The most frequently used surgical approach was a preseptal transconjunctival approach. An overall decrease of gaze restriction (93%), diplopia (89%) and enophthalmos (86%) was observed. According to the fracture size, we used Ethisorb patches in smaller fractures and resorbable or titanium meshes or autologous bone in larger fractures in most cases. Patients who underwent surgery more than 7 days after the trauma showed better results with regard to an improvement of diplopia and motility disturbances than patients who were treated immediately. In indicated cases, the surgical repair of OFF leads to very good results if the anatomical and functional properties of the orbit and its contents are respected. The applied strategy and means presented in our study proved of value and can therefore be recommended.

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