Role of Ca2+-independent phospholipase A2 and n-3 polyunsaturated fatty acid docosahexaenoic acid in prostanoid production in brain: perspectives for protection in neuroinflammation.

Various diseases of the central nervous system are characterized by induction of inflammatory events, which involve formation of prostaglandins. Production of prostaglandins is regulated by activity of phospholipases A(2) and cyclooxygenases. These enzymes release the prostaglandin precursor, the n-6 polyunsaturated fatty acid, arachidonic acid and oxidize it into prostaglandin H(2). Docosahexaenoic acid, which belongs to the n-3 class of polyunsaturated fatty acids, was shown to reduce production of prostaglandins after in vivo and in vitro administration. Nevertheless, the fact that in brain tissue cellular phospholipids naturally have a uniquely high content of docosahexaenoic acid was ignored so far in studies of prostaglandin formation in brain tissue. We consider the following possibilities: docosahexaenoic acid might attenuate production of prostaglandins by direct inhibition of cyclooxygenases. Such inhibition was found with the isolated enzyme. Another possibility, which has been already shown is reduction of expression of inducible cyclooxygenase-2. Additionally, we propose that docosahexaenoic acid could influence intracellular Ca(2+) signaling, which results in changes of activity of Ca(2+)-dependent phospholipase A(2), hence reducing the amount of arachidonic acid available for prostaglandin production. Astrocytes, the main type of glial cells in the brain control the release of arachidonic acid, docosahexaenoic acid and the formation of prostaglandins. Our recently obtained data revealed that the release of arachidonic and docosahexaenoic acids in astrocytes is controlled by different isoforms of phospholipase A(2), i.e. Ca(2+)-dependent phospholipase A(2) and Ca(2+)-independent phospholipase A(2), respectively. Moreover, the release of arachidonic and docosahexaenoic acids is differently regulated through Ca(2+)- and cAMP-dependent signal transduction pathways. Based on analysis of the current literature and our own data we put forward the hypothesis that Ca(2+)-independent phospholipase A(2) and docosahexaenoic acid are promising targets for treatment of inflammatory related disorders in brain. We suggest that Ca(2+)-independent phospholipase A(2) and docosahexaenoic acid might be crucially involved in brain-specific regulation of prostaglandins.     

High affinity neurotrophin receptors in the human pre-term newborn, infant, and adult cerebellum

The immunohistochemical occurrence of the high affinity neurotrophin (NT) receptors trkA, trkB, and trkC is shown in the pre-term newborn, infant, and adult human post-mortem cerebellum. Immunoreactive neuronal perikarya and processes were observed in all specimens examined, where they appeared unevenly distributed in the cerebellar cortical layers and deep nuclei, and showed regional differences among cerebellar lobules and folia. The trk receptor-antibodies, tested by Western blot on human cerebellum homogenates, revealed multiple immunoreactive bands for trkA and single bands for trkB and trkC. The results obtained show the tissue localization of the trk receptor-like immunoreactivity in the human cerebellum from prenatal to adult age. The analysis for codistribution of the receptors with the relevant ligand and among the receptors in discrete cortical and deep nuclei tissue fields shows a wide variety of conditions, from a good similarity in terms of type and density of labeled structures, to a lack of correspondence, and suggests the possibility of colocalization of trk receptors with the relevant neurotrophin and among them in the cerebellar cortex. These results sustain the concept that the neurotrophin trophic system participates in the development, differentiation, and maintenance of the human cerebellar connectivity and support the possibility of a multifactorial trophic support for the neurotrophins through target-derived and local mechanisms.     

Propriospinal myoclonus after treatment with ciprofloxacin.

The clinical and electrophysiological features of a truncal myoclonus in a 55-year-old man are described. The electromyographic characteristics point toward propriospinal myoclonus. It is suggested that a myoclonic generator was released after use of ciprofloxacin, by antagonising the gamma-aminobutyric acid metabolism.     

Chronic peritoneal dialysis in paediatrics: Experience of a national registry

The results of the first 3 year' collaboration of the Italian Registry of Paediatric Chronic Peritoneal Dialysis (CPD) (1986–1988) are presented. This Registry acquired data on the majority of the paediatric patients treated with CPD in Italy, thus providing a national picture in a field where few nationwide surveys are available. Patients of less than 15 years of age at the start of dialysis were enrolled and clinical data collected until the age of 19 years. The number of nephrological paediatric centres participating in the Registry increased from 7 in 1986 to 11 in 1988. The total number of patients on CPD was 70 and the percentage of dialysed children treated with CPD ranged from 40.2% to 43.6%. Data on 89 peritoneal catheters were collected: during 1417 dialysis-months 70 catheter-related complications were observed (1:20.8 dialysis-months); actuarial catheter survival was 92.7% at 6 months, 84.8% at 1 year and 68.8% at 2 years. The incidence of peritonitis changed from 1 episode every 10.9 patient-months in 1986 to 1 every 19.8 in 1988. Abdominal hernias were the other main clinical complication observed. The survival of patients was 92.5% at 3 years, while the technique survival at the same time was 84%.     

Endothelin-1 in children with chronic renal failure

Endothelin-1 (ET-1) was meansured after extraction from plasma of normal adults (5.9±1.9 pg/ml,n=22), normal children (7.1±1.86 pg/ml,n=29), nonhaemodialysed children with chronic renal failure (CRF) (11.1±1.8 pg/ml),n=10), renal graft recipients (9.5±3.4 pg/ml,n=37), haemodialysed children 24 h after a haemodialysis session (20.02±10.9 pg/ml,n=26) and haemodialysed children before and after a haemodialysis session (15.31±10.6 and 13.8±8.5 respectively,n=14). A sensitive and specific radioimmunoassay was used. ET-1 was significantly higher in non-haemodialysed CRF children and in renal graft recipients than in normal children (P<0.001 andP<0.01, respectively) and significantly higher in haemodialysed children when compared with normal children, non-haemodialysed CRF children and renal graft recipients (P<0.001). ET-1 concentrations were similar in normal children and normal adults. ET-1 was inversely correlated with glomerular filtration rate in non-haemodialysed CRF children (r=–0.39,P<0.01) and positively correlated with extracellular volume in haemodialysed children (r=0.435,P<0.03). After haemodialysis, ET-1 increased in 6 and decreased in 8 of the 14 children studied before and after a haemodialysis session.     

Oral leiomyosarcomas: report of two cases with immunohistochemical profile.

Leiomyosarcoma of the oral cavity is a very rare tumor associated with aggressive clinical behavior and low survival. In this paper, we report 2 cases of leiomyosarcoma, affecting the gingival mucosa of a 54-year-old female and the maxillary bone of a 63-year-old male. Histologically, the tumors were composed of variably oriented fascicles of spindle-shaped cells with cigar-shaped nuclei and eosinophilic cytoplasm. The lesions were treated by surgical resection. Immunoreactivity to anti-vimentin, anti-smooth muscle actin, anti-desmin, anti-laminin, and anti-muscle-specific actin antibodies were found; conversely, the tumor cells were negative for anti-S100 and AE1/AE3 proteins. This report emphasizes the role of immunohistochemical study for correct diagnosis of leiomyosarcoma.     

Peripheral Foot Blockade Versus Popliteal Fossa Nerve Block: A Prospective Randomized Trial in 51 Patients

The majority of foot and ankle operations are performed on an outpatient basis and often under some form of regional anesthesia. In this prospective, randomized study of 51 patients undergoing elective unilateral forefoot procedures, we compared 2 different anesthetic techniques: the peripheral foot blockade and the popliteal sciatic nerve block. Variables assessed included the quality of surgical anesthesia, postoperative analgesia, and the incidence of postoperative complications. The anesthesia was classified as effective if it was the sole anesthetic technique for the forefoot surgery. We found successful results in both groups: 92% in the foot block group and 96% in the popliteal block group. Analysis of time required to perform the anesthetic procedure showed a significant difference between the 2 groups, with foot block being considerably faster (14.3 minutes vs 19.2 minutes for popliteal block) (P = .0078). Foot block patients demonstrated 10.96 hours of analgesia, whereas popliteal block patients exhibited 14.32 hours (P = .132). With a mean follow-up of 5.7 months, we did not find anesthesia-related complications in any of the patients. Both techniques showed a high level of safety and efficacy, with no significant difference detected between them. Our patients showed a high rate of satisfaction with both procedures (96% for foot block patients and 96.1% for popliteal block patients) and reported a good discharge disposition. These data show that both procedures are safe and effective anesthetic techniques and well suited to forefoot ambulatory surgery.     

Tape-stripping method in man: comparison of evaporimetric methods

BACKGROUND/PURPOSE: If the occlusion time of a closed chamber evaporimeter on the skin is too long, saturation might occur. We previously compared an open chamber and a closed chamber device on healthy volunteers. Comparable data on stripped skin with higher evaporation rates are not available. This study compares the sensitivity and correlation of open and closed chamber devices in a tape-stripping human model. The amount of tape removed SC was also quantified with a protein assay method. METHODS: Ten healthy volunteers (six male and four female; seven Caucasians and three Asian; mean age 38+/-16) were enrolled. In a randomized manner, one forearm was measured by an open chamber device and the opposite by a closed chamber device. After recording baseline measurements, 20 strippings were taken on each test site with tape disks. Transepidermal water loss (TEWL) was measured at the end of 10 and 20 tape strippings at each test site. Stratum corneum (SC) aggregates in the strips was assayed. RESULTS: The mean values obtained from two devices were similar after 10 trips and 20 strips. There was no statistically significant difference. The closed chamber device showed a slightly higher (but not significant) inter-individual coefficient of variation. SC aggregates in the strips were similar and without a statistically significant difference. CONCLUSION: The study suggests that both devices might yield similar TEWL values on stripped human skin in vivo.     

Techniques for high-resolution MR imaging of atherosclerotic plaque

Atherosclerotic cardiovascular disease is the most common cause of death in the United States. Investigation of atherosclerotic plaque morphology and composition is important because the findings may be useful in predicting prognosis or response to therapy. This study presents high-resolution magnetic resonance (MR) imaging techniques developed on a 1.5-T whole-body imager with a custom-built surface coil, for characterizing the composition and morphology of plaque removed at carotid endarterectomy. The initial comparison of MR imaging and histologic results showed good correlation. In conjunction with MR angiography, these techniques could be used in in vivo imaging to define the size, location, and contents of atherosclerotic plaque at the carotid bifurcation.     

Neurotrophin-like immunoreactivity in the human pre-term newborn, infant, and adult cerebellum

The immunohistochemical occurrence of the neurotrophin (NT) proteins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3) is shown in the pre-term newborn, infant, and adult human post-mortem cerebellum. The NT-like immunoreactive structures were unevenly distributed and showed regional differences among cerebellar lobules and folia. NGF-, NT-4-, and NT-3-positive neuronal perikarya were observed in all specimens examined. At variance with the other neurotrophins, the BDNF antiserum labelled neuronal cell bodies only in newborn life and infancy, as well as extensive nerve fibre systems, whose density increased with age. The NT-antibodies, tested by Western blot on human cerebellum homogenates, revealed immunoreactive bands corresponding to proteins of heterogenous molecular weight. The results obtained provide a first demonstration of the tissue localization of the NTs in the human cerebellum from perinatal to adult age, thus suggesting their involvement in the development, differentiation and maintenance of the cerebellar connectivity. Codistribution of the four NTs or sets of them was observed in cortical and deep nuclei neurons. Multiple trophic roles for NTs, encompassing the classic target-derived and local mechanisms of support, are envisaged as significant in development, differentiation, and maintenance of the human cerebellar connectivity.