Potential usefulness of basic fibroblast growth factor as a treatment for stroke

Within the past few years, a growing body of evidence has accumulated indicating that exogenously administered neurotrophic growth factors may limit the extent of acute ischemic neural injury and enhance functional neurorecovery following stroke. One of the most widely studied growth factor in this regard is basic fibroblast growth factor (bFGF). In preclinical studies, bFGF administered intravenously within hours after the onset of ischemia reduces infarct size, presumably due to direct protection of cells at the borders (penumbra) of cerebral infarction. On the other hand, if bFGF is administered intracisternally starting at one day after ischemia, infarct size is not reduced, but recovery of sensorimotor function of the impaired limbs is increased, presumably due to enhancement of new neuronal sprouting and synapse formation in the intact uninjured brain. Clinical trials of the intravenous administration of bFGF as a cytoprotective agent in acute stroke are in progress. Trials of the delayed administration of bFGF as a recovery-promoting agent in subacute stroke are anticipated.     

Inhibitory effect of capsaicin on cholinergic transmission in ovine airways: evidence for non-cholinergic contractions

Electrical stimulation of ovine trachealis smooth muscle and bronchial ring segments induced neurogenic and monophasic atropine-sensitive contractions. Pretreatment of the tissues with capsaicin (100 microM) significantly reduced these contractions indicating a possible contribution of a peptidergic neurotransmitter to the contractions. The effect of capsaicin on electrically induced contractions was significantly inhibited by capsazepin indicating an action on vanilloid receptors. In both preparations, electrically induced contractions were not modified by tachykinin NK(1)- and NK(2)-receptor antagonists singly and in combination. It was therefore concluded that a component of the atropine-sensitive electrically induced contractions of ovine airways smooth muscles involved the release of a peptide neurotransmitter which is probably not a tachykinin. However, an action of capsaicin on prejunctional vanilloid receptors located on cholinergic nerves cannot be ruled out.     

Clostridium difficile acquisition rate and its role in nosocomial diarrhoea at a university hospital in Turkey

Infection with Clostridium difficile can present with various clinical pictures ranging from an asymptomatic carrier state to pseudomembranous colitis and plays an important part in the etiology of nosocomial diarrhoea. To identify risk factors for C. difficile colonization and diarrhoea in hospitalized subjects, patients admitted to a general medicine ward at Marmara University hospital during a one year period were entered into the study. Of the 202 patients, nosocomial diarrhoea developed in 45 (22.3%). Fourteen patients (6.9%) were colonized with C. difficile during their hospitalization period. Ten of the colonized patients (71.4%) developed diarrhoea and were found to be positive by toxin assay. Pseudomembranous colitis was confirmed endoscopically in 3 of the patients with diarrhoea. Administration of beta lactam agents such as ampicillin and cephalosporins; gastrointestinal manipulations and admission to the intensive care unit were found as major risk factors for C. difficile colonization.     

Huge colloid cyst of the third ventricle associated with calcification in the cyst wall

Giant or huge colloid cysts of the third ventricle up to of more than 3 cm in diameter are extremely rare. The patient presented with symptoms of increased intracranial pressure, including headache, vomiting, and papilledema. Computerized tomographic (CT) scan revealed a hypodense, huge colloid cyst of the third ventricle associated with calcification in the cyst wall. Both hypodensity and calcification are uncommon roentgenological findings for colloid cysts of the third ventricle. The patient was operated on by the transcortical/transventricular approach and the colloid cyst was completely excised.     

Dietary antioxidants and the biochemical response to oxidant inhalation. II. Influence of dietary selenium on the biochemical effects of ozone exposure in mouse lung

We examined the influence of dietary selenium (Se) on the pulmonary biochemical response to ozone (O3) exposure. For 11 weeks, weanling female strain A/St mice were fed a test diet containing Se either at 0 ppm (-Se) or 1 ppm (+Se). Each diet contained 55 ppm vitamin E (vit E). Mice from each dietary group were exposed to 0.8 +/- 0.05 ppm (1568 +/- 98 micrograms/m3) O3 continuously for 5 days. After O3 exposure, they were killed along with a matched number of unexposed controls, and their lungs were analyzed for various biochemical parameters. The Se contents of lung tissue and whole blood were determined, and the levels were seven- to eightfold higher in +Se mice than in -Se mice, reflecting the Se intake of the animals. In unexposed control mice, Se deficiency caused a decline in glutathione peroxidase (GP) activity relative to +Se group. After O3 exposure, the GP activity in the -Se group was associated with a lack of stimulation of glutathione reductase (GR) activity and the pentose phosphate cycle (PPC) as assessed by measuring glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) activities. In contrast, the +Se group after O3 exposure exhibited increases in all four enzyme activities. Other parameters, e.g., lung weight, total lung protein, DNA and nonprotein sulfhydryl contents, and O2 consumption, were not affected by dietary Se in the presence or absence of O3 exposure. The data indicate that dietary Se alters the GP activity, which in turn influences the GR and PPC activities in the lung evidently through a reduced demand for NADPH. The level of vit E in the lung was found to be twofold higher in the -Se group than in the +Se group, suggesting a compensatory relationship between Se and vit E in the lung. With O3 exposure, both Se and vit E contents further increased in the lungs of each dietary group. It is plausible that Se and vit E under oxidant stress are "mobilized" to the lung from other body sites.     

Matching pain coping strategies to the individual: A prospective validation of the Cognitive Coping Strategy Inventory

The validity of the Cognitive Coping Strategy Inventory (CCSI; Butler et al., 1989) was tested in a prospective fashion. Subjects were randomly assigned to one of three conditions. Some were matched to a strategy for which they received a high CCSI score, some were mismatched to a strategy for which they received a low CCSI score, and some were given a choice of strategies. Those subjects using a matched strategy obtained better threshold and tolerance times on the cold pressor than subjects who used a mismatched strategy. Despite clear differences in exposure to the cold pressor these conditions did not differ from each other in self-reported levels of pain. It was concluded that the CCSI appears to be a valid and useful tool for selecting a coping strategy to help particular individuals manage acute pain. Though the CCSI is relatively easy to administer and score, the comparative costs and benefits of using it must be weighed against the somewhat more efficient approach of simply offering the subject a choice of treatments. Subjects given a choice of strategies performed as well as subjects matched to a strategy on the basis of CCSI scores.     

Gamete development inPlasmodium berghei regulated by ionic exchange mechanisms

Ionic regulation in the induction of exflagellation ofPlasmodium berghei was investigated by culturing the parasites in various isotonic media. Of the salts tested, NaHCO₃ exhibited the highest activity in inducing exflagellation, whereas KHCO₃ showed no activity. In the absence of HCO ₃ ^– , media containing monovalent cation (Na⁺, K⁺, Cs⁺, Rd⁺, choline⁺, lysine⁺, arginine⁺) and Cl^– also induced exflagellation, but their activities were lower than that of NaHCO₃. Anions of Br^– or NO ₃ ^– could be substituted with Cl^–, whereas other anions such as I^–, NO ₂ ^– , SO ₄ ^2– , SCN^–, H₂PO ₄ ^– , or HPO ₄ ^2– failed to induce exflagellation, as did tetramethylammonium-Cl, CaCl₂, MgSO₄, MgCl₂ and sucrose as well. These results suggest that the induction of exflagellation requires the presence of Na⁺ and HCO ₃ ^– or monovalent, membrane-permeable cation and Cl^– in the medium. Measurements of the efflux of H[¹⁴C]O ₃ ^– or Cl^– indicated that these anions were released from the cells into the NaCl or the NaHCO₃ medium, respectively, probably by exchange in HCO ₃ ^– /Cl^–. Determination of intracellular ionic concentrations by electron microscopic X-ray microanalysis of cryopreserved specimens revealed that in the NaHCO₃ medium, external Na⁺ (and probably HCO ₃ ^– ) enters the gametocytes by exchange with internal Cl^– (and probably H⁺), whereas in Cl^–-containing media, external unspecified cation and Cl^– influx by exchange, probably with H⁺ and HCO ₃ ^– . It is therefore suggested that two separate ion exchangers, i.e., Na⁺-dependent HCO ₃ ^– (in)/Cl^–(out) and nonspecific monovalent-cation-dependent Cl^–(in)/HCO ₃ ^– (out) exchangers, are involved in the induction of gametogenesis inP. berghei. Furthermore, the presence of both classes of anion in the medium enhanced exflagellation activity and increased Na⁺ uptake more than did the NaCl or NaHCO₃ medium alone. The apparent synergistic enhancement by two contraactive anion exchangers is consistent with a recycling model of pH_i regulation, in which HCO ₃ ^– and Cl^– are exchanged between the cells and the media, resulting in the acceleration of monovalent cation/H⁺ exchange.This work was supported by a Grant-in-Aid (No. 01570212) from the Ministry of Education, Science and Culture, Japan and the Ohyama Health Foundation, Japan (to FK), and in part by the Medical Research Council, United Kingdom (to RES)     

Contradictory effects of chlorpromazine on endothelial cells in a rat model of endotoxic shock in association with its actions on serum TNF-alpha levels and antioxidant enzyme activities.

We examined the effects of the phenothiazine derivative, chlorpromazine on thoracic aortic endothelial cell histology (14 h after LPS challenge) in a model of endotoxic shock in rats. Since excessive formation of tumor necrosis factor-alpha (TNF-alpha) and oxygen-derived free radicals contribute to endothelial injury in endotoxemia, we also evaluated the effect of the drug on the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase in liver tissue in this model and tried to find out whether this possible effect was associated with a change in serum TNF-alpha levels (measured 90 min after chlorpromazine administration). Endotoxemia was induced by a single i.p. injection of lipopolysaccharide (LPS) (5 mg kg(-1) in 1.5 ml of saline; LPS from Escherichia coli serotype 055:B5, L-2880, Sigma Chemical Company). Electron microscopic evaluation of the aortas revealed that chlorpromazine (administered 30 min prior to LPS challenge), in smaller doses (3 mg kg(-1)) ameliorated the endothelial cell injury caused by LPS, whereas it caused deterioration of endothelial cell morphology in higher doses (10 and 25 mg kg(-1)). Chlorpromazine administration caused a significant reduction in serum TNF-alpha levels, which was correlated well with an increase in SOD activity in all drug doses (3, 10 and 25 mg kg(-1)). Catalase activity was increased only in the 25 mg kg(-1) chlorpromazine group.