Measurements in the peripheral retina using LDF and laser interferometry are mainly influenced by the choroidal circulation

PURPOSE: Two laser based methods for the assessment of ocular hemodynamics in humans have been investigated: laser Doppler flowmetry (LDF) and laser interferometric measurement of fundus pulsation amplitude (FPA). When the laser with either of the two methods is focused onto the fovea it is obvious that only choroidal blood flow contributes to the signals. When the laser is, however, directed to other parts of the retina the situation is more complex. Whereas the retina shows a pronounced vasoconstrictor response to systemic hyperoxia the effect in the choroid is small. We therefore investigated the effect of 100% O2 breathing on results as obtained with the above mentioned techniques at different fundus locations. METHODS: Twelve healthy subjects were included. Four 15-minutes 100% O2 breathing periods were scheduled for each subject. During two of these breathing periods LDF was performed at the fovea (ChBFf) and at a fundus location approximately 7.5 degrees nasally to the fovea (ChBFp), respectively. During the other two periods FPA was assessed at the same fundus locations (FPAf, FPAp). RESULTS: ChBFf tended to decrease during 100% oxygen breathing (6 +/- 4%), but this effect was not significant. The decrease in ChBFp (10 +/- 4%), was comparable. FPAf (10 +/- 2%; P < 0.001) and FPAp (13 +/- 2%; P < 0.001) decreased significantly during systemic hyperoxia, but again there was no difference in the response obtained at the two fundus locations. CONCLUSION: When LDF and FPA are applied at the peripheral retina the obtained signal is mainly influenced by the choroidal circulation.     

Effects of amifostine on liver oxidative stress caused by cyclophosphamide administration to rats

Cyclophosphamide is an inactive cytostatic, which is metabolised into active metabolites mainly in the liver. During bioactivation, reactive oxygen species (ROS) are also formed, which can modify the components of both healthy and neoplastic cells leading to decreased antioxidative capacity. Amifostine is a drug that can inactivate ROS. The aim of the present study was to evaluate the influence of amifostine on the antioxidative system of the liver of rats exposed to cyclophosphamide. Intraperitoneal administration of cyclophosphamide was found to decrease the activity of liver antioxidative enzymes, i.e. superoxide dismutase, glutathione peroxidase and glutathione reductase, and to increase catalase activity. Amifostine slightly influenced antioxidative enzyme activity, causing a significant increase only in superoxide dismutase activity. Co-administration of cyclophosphamide and amifostine nearly prevented changes in activities of superoxide dismutase, glutathione reductase and catalase, as well as to a high degree of glutathione peroxidase. Cyclophosphamide also evoked a decrease in the level of non-enzymatic antioxidants, such as reduced glutathione and vitamins C, E and A, as well as total antioxidant status. Administration of amifostine alone caused a significant increase in non-enzymatic antioxidant level that resulted in an increase in total antioxidant status. Administration of amifostine together with cyclophosphamide to a large extent prevented changes in the evaluated non-enzymatic antioxidative parameters, decreasing values of their concentration to the values of control group. Changes of liver antioxidative abilities during detoxification of cyclophosphamide were accompanied by intensified lipid peroxidation, manifested by an increase in concentration of products such as malondialdehyde and 4-hydroxynonenal. Amifostine caused the inhibition of lipid peroxidation in the liver of both control and cyclophosphamide-treated rats. In conclusion, our results suggest that amifostine significantly protects liver antioxidant properties from changes caused by cyclophosphamide treatment and in consequence prevents oxidative stress and phospholipid peroxidative damage.     

Tuberculosis of the central nervous system: case reports

Tuberculosis of the central nervous system possess a serious clinical and radiological problem, since early treatment of this condition is crucial for the patient's life, and tuberculous process in the CNS may mimic many other pathologies. In this paper three cases of tuberculous process difficult to diagnose are presented. In all the cases early treatment could be started due to MRI findings suggesting tuberculous etiology. The authors emphasize the importance of presumptive radiological diagnosis in reducing the morbidity and mortality rates due to CNS tuberculosis.     

Neuroimaging in a chronic demyelination process following tick-borne encephalomyelitis

We present a case of a 17-year-old female patient with a tick-borne neuroinfection. Tick-borne encephalitis is a viral disease of the CNS. Tick-borne encephalitis is usually of diphasic type, with partial epileptic seizures. No such symptoms were observed in this case. Since areas of demyelination could be seen on CT and MRI scans, immunological etiology should be taken into consideration. The correct diagnosis was established on the basis of serological examination and neuroimaging findings.     

Propranolol and atropine do not alter choroidal blood flow regulation during isometric exercise in healthy humans

Recent studies indicate that the human choroid has a considerable capacity to keep blood flow constant despite exercise-induced increases in perfusion pressure. The mechanisms underlying this vasoconstrictor response remain unclear. We hypothesized that pharmacological modulation of the autonomic nervous system may alter the choroidal pressure/flow relationship during squatting. To test this hypothesis, we performed a randomized, double-masked, placebo-controlled, three-way crossover study in 15 healthy male volunteers. Subjects received, on different study days, intravenous infusions of the beta-adrenoceptor antagonist propranolol, the muscarinic receptor antagonist atropine, or placebo. During these infusions, subjects performed squatting for 6 min. Choroidal blood flow was assessed with laser Doppler flowmetry and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure. As expected, propranolol reduced basal pulse rate, whereas atropine increased pulse rate, indicating that the drugs were administered at systemically effective doses. None of the drugs altered the choroidal pressure/flow relationship during isometric exercise. These data indicate that the regulatory vasoconstrictor capacity of the choroid during exercise is not affected by systemic blockade of beta-adrenoceptors or muscarinic receptors.     

Suppressed clinical experimental autoimmune myasthenia gravis in bm12 mice is linked to reduced intracellular calcium mobilization and IL-10 and IFN-gamma release by acetylcholine receptor-specific T cells

Class II MHC mutant bm12 mice have an increased resistance to experimental autoimmune myasthenia gravis (EAMG) compared to C57BL/6 mice. In vitro, this relative resistance was mainly associated with a reduced cytokine response to acetylcholine receptor (AChR) and its dominant pathogenic peptide alpha 146-162, whereas the response to the epitope alpha 111-126 remained intact. Calcium mobilization after stimulation of AChR-immune T cells with AChR or alpha 146-162 peptide, but not alpha 111-126 peptide, was decreased in bm12 compared to C57BL/6. Thus, the reduced incidence of clinical EAMG in bm12 is linked to lower IFN-gamma and IL-10 release, and intracellular calcium mobilization by alpha 146-162-specific T cells.     

Contribution of interleukin 2 and interleukin 12 receptors in signal transduction during cell activation of the immune system

Interleukin-2 (IL-2) and interleukin-12 (IL-12) belong to lympho-hematopoietic cytokines and play a critical role in the promotion and enhancement of cellular response. IL-2 as the second signal of antigenic stimulation facilitates the transition of the cell cycle from phase G1 to phase S and is responsible for the regulation of T lymphocytes proliferation and the activation of cytotoxic T cells, natural killers, macrophages and granulocytes. IL-12 is the dominant factor in T helper cells polarization leading to the secretion of IFN-gamma. Receptors for both of the cytokines (IL-2R or IL-12R) represent class I cytokine receptors composed of multiple subunits. Generally, they contain a similar extracellular conserved motif of four cysteines, and amino acid sequence--WSXWS (interacting directly with ligand) but possess no catalytic domens in the intrinsic tail of the chains. For this reason, to transfer the impact, the association with number of signaling molecules, allowing the activation of the signaling pathways is required. The connections of IL-2R or IL-12R with their ligands recruit receptor-associated cytoplasmic proteins from the JAK family (JAK1/JAK3 or JAK2/TYK2, respectively), which catalyze the phosphorylation of themselves and intrinsic tyrosine residues on the receptor, creating STAT docking sites. This phosphorylated and subsequent dimerised proteins bind rapidly to DNA and activate it. This review, presents the differences and similarities between the signaling pathways triggered by IL-2R or IL-12R ligation.     

N-methyl-d-aspartate receptor-mediated processing of beta-amyloid precursor protein in rat hippocampal slices: in vitro--superfusion study

Abnormal proteolytic degradation of the beta amyloid precursor protein (beta-APP) may result in accumulation of potentially neurotoxic beta amyloid (betaA). The role of various receptors in the regulation of beta-APP processing has been suggested. This study aimed to determine how NMDA receptors and Ca2+ ions regulate proteolysis of beta-APP in rat hippocampus in vitro. Adult rat hippocampal slices were superfused with NMDA-containing media, and immunoreactivity of soluble beta-APP derivatives was detected in dialysates. Application of 100 microM and 250 microM NMDA for 20 min in Ca2+-containing medium induced dose-dependent release of aminoterminal beta-APP derivatives, and a fragment of Abeta sequence, whereas carboxy-terminal fragments of beta-APP were only slightly detected. This indicates activation of beta-APP processing, and release of its soluble cleavage products. This effect was inhibited by NMDA receptor antagonist 1 microM MK-801 and 100 microM CPP in Ca2+-free medium, thus indicating that NMDA receptors and calcium ions mediate proteolytic non-amyloidogenic degradation of the beta-APP.     

The role of platelet activating factor (PAF) in physiology and pathology of the central nervous system

This review describes the role of platelet activating factor (PAF) in the central nervous system injury. Cerebral ischaemia, traumatic injury of central nervous system, metabolic, toxic and degenerative neuropathy, and also the increase in Ca2+ concentration in the cell, are strong stimulators of PAF synthesis and its release from cell membranes. Neurons, glial and microglial cells, monocyte cell populations, macrophages and endothelial cells of blood vessels are the targets of platelet activating factor. The release of PAF leads to ischaemia of nervous tissue, acute traumatic or nontraumatic injuries, degenerative and metabolic nervous system disorders in adults. The use of PAF receptor antagonists prevents partially cell injury in central nervous system and leukocyte adhesion to endothelial cells.