ATP downregulation in mononuclear cells from children with graft-versus-host disease following extracorporeal photochemotherapy

Graft-versus-host disease (GvHD) is a frequent and major complication of allogeneic bone marrow transplantation(BMT). Acute GvHD occurs in 40% to 50% of allogeneic BMT recipients; chronic GvHD can be observed in 30% to 60% of long-term survivors.     

The stiff-person syndrome. Case report

The stiff-person syndrome is a rare and disabling disorder, characterized by muscle rigidity with superimposed painful spasms involving axial and limb musculature. The clinical symptoms are continuous contraction of agonist and antagonist muscles caused by involuntary motor-unit firing at rest and the spasms that are precipitated by tactile stimuli, passive strach, volitional movement of affected or unaffected muscles, startling noises and emotional stimuli. Both the rigidity and the spasms are relieved by sleep, general anaesthesia, myoneural blockade and peripheral nerve blockade. The cause of the stiff-person syndrome is unknown but an autoimmune pathogenesis is suspected because 1) the presence in the cerebrospinal fluid (CSF) of antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the synthesis of the inhibitory neurotrasmitter gamma-aminobutyric acid (GABA), 2) the association of the disease with other autoimmune disorders, 3) the presence of various autoantibodies and 4) a strong immunogenetic association. The stiff-person syndrome is clinically elusive but potentially treatable and should be considered in patients with unexplained stiffness and spasms. Drugs that enhance GABA neurotransmission, such as diazepam, vigabatrin and baclofen, provide modest relief of clinical symptoms. Immunomodulatory agents such as steroids, plasmapheresis and intravenous immunoglobulin, seem to offer substantial improvement.     

Time-dependent induction of anxiogenic-like effects after central infusion of urocortin or corticotropin-releasing factor in the rat

RATIONALE: Corticotropin-releasing factor (CRF) and urocortin (Ucn) belong to the CRF-related family, share a high degree of structural homology and bind to CRF receptors. However, compared with CRF, Ucn was shown to display either weaker or similar anxiogenic-like effects in vivo. OBJECTIVE: To compare the anxiogenic-like responses of rats injected intracerebroventricularly (ICV) with different doses of either rat/human CRF (r/hCRF) or rat Ucn (rUcn) at different intervals after injection. METHODS: Rats were tested on three validated paradigms of emotional behavior [i.e. elevated plus-maze (EPM), defensive withdrawal (DW) and conflict test (CT)] 5 and 30 min after treatment. RESULTS: In the EPM test only r/hCRF, but not rUcn, produced anxiogenic-like effects at the dose of 1.0 microg, when the peptides were injected 5 min before testing. At 30 min after injection, both peptides caused a significant reduction of open arms exploration, rUcn being effective at 0.01 microg. In the DW test both peptides were equally potent in decreasing the exploratory behavior and increasing the time spent in the chamber at the dose of 1.0 microg when tested 30 min after injection. In the CT both rUcn (0.25-1.0 microg) and r/hCRF (0.75-1.0 microg) decreased significantly the responding in the punished component. However, rUcn reduced food responding also in the unpunished component possibly due to its powerful anorectic activity. CONCLUSIONS: Comparison of anxiogenic-like activities of r/hCRF and rUcn at doses up to 1.0 microg revealed striking differential effects that depended on the time of testing after ICV peptide injection, and on the paradigm of anxiety used. These results suggest that the onset of r/hCRF and rUcn actions related to behavioral responses to anxiety is likely to depend on brain peptide-specific mechanisms including binding properties to CRF-receptors, differential distribution to specific functional brain sites and the distribution and effectiveness of binding-protein interactions.     

Asthma -- a need for a rethink?

Asthma is a major medical problem but, despite decades of research, the mechanisms that underlie this condition remain elusive. Although the eosinophil has been regarded as a cell that is central to the pathogenesis of asthma, the failure to abrogate asthma symptoms by novel treatments that are designed to suppress the recruitment of eosinophils to the airways challenges this dogma. Our approach to understanding bronchial asthma needs to be broadened to include alterations in the function of afferent nerves that supply airways. Changes in the activity of these nerves offer a possible mechanism by which asthmatic subjects are uniquely responsive to a wide range of physiological and chemical stimuli. Here, we review the current status of asthma research.     

Real-time measurement of indoor particulate matter originating from environmental tobacco smoke: a pilot study

Short-term measurement of suspended particulate matter has been recently made possible since the release of laser-operating portable instruments. Data of a pilot study of field evaluation of environmental tobacco smoke (ETS) with a portable instrument are reported. We analysed the concentrations of total suspended particle (TSP) and of the fine particles PM10, PM7, PM2.5 and PM1 released indoor from a single cigarette, and their levels inside smoking- and non-smoking-areas of a restaurant. The results indicate that ETS creates high level indoor particulate pollution, with concentrations of PM10 exceeding air quality standards. This kind of field evaluation could allow a more careful assessing of short-term exposure to ETS and its relevance to public health.     

Characterization of the anandamide induced depolarization of guinea-pig isolated vagus nerve

1. There is considerable interest in elucidating potential endogenously derived agonists of the vanilloid receptor and the role of anandamide in this regard has received considerable attention. In the present study, we have used an electrophysiological technique to investigate the mechanism of activation of vanilloid receptors in an isolated vagal preparation. 2. Both capsaicin and anandamide depolarized de-sheathed whole vagal nerve preparations that was antagonized by the VR1 antagonist, capsazepine (P<0.05) whilst this response was unaltered by the cannabinoid (CB1) selective antagonist SR141716A or the CB2 selective antagonist, SR144528, thereby ruling out a role for cannabinoid receptors in this response. 3. The PKC activator, phorbol-12-myristate-13-acetate (PMA) augmented depolarization to both anandamide and capsaicin and this response was significantly inhibited with the PKC inhibitor, bisindolylmaleimide (BIM) (P<0.05). 4. The role of lipoxygenase products in the depolarization to anandamide was investigated in the presence of the lipoxygenase inhibitor, 5,8,11-Eicosatriynoic acid (ETI). Depolarization to anandamide and arachidonic acid was significantly inhibited in the presence of ET1 (P<0.05). However, in the absence of calcium depolarization to anandamide was not inhibited by ETI. 5. Using confocal microscopy we have demonstrated the presence of vanilloid receptors on both neuropeptide containing nerves and nerves that did not stain for sensory neuropeptides. 6. These results demonstrate that anandamide evokes depolarization of guinea-pig vagus nerve, following activation of vanilloid receptors, a component of which involves the generation of lipoxygenase products. Furthermore, these receptors are distributed in both neuropeptide and non-neuropeptide containing nerves.     

Humoral and cellular immunity against Cryptosporidium infection

Protozoans of the genus Cryptosporidium are the etiological agents of opportunistic infections mainly of the gastrointestinal tract of animals and humans. Young and elderly persons, those with concomitant infections, with AIDS, under an immunosuppressive therapy, with congenital T-cell, B-cell or other effector cell deficiencies develop persistent progressive infections of different degree of severity related to the level of immunodepression. Both humoral and cellular immunity play a role in the control of this infection, but the latter plays the major role, mainly in the intestinal mucosa. However, a natural resistance to these coccidian parasites is also involved. IgG, IgM and IgA have been detected in serum and mucosa of humans and animals with the resolution of the infection; but also high levels of these immunoglobulins have been detected in persons with AIDS with chronic cryptosporidiosis. In HIV-positive persons, CD4+ T-cells are required to prevent the establishment of the infection and IFN-gamma and CD4+ T-cells can also limit the duration and the clinical manifestations of the infection. In persons exposed to cryptosporidial infections, it has been possible to show the important role of IFN-gamma in both the innate and acquired cell mediated immunity. The severity of cryptosporidiosis has been also associated with the inability to produce IFN-gamma. An antibody therapy using bovine colostrum from cows hyperimmunised with Cryptosporidium oocysts or monoclonal antibodies against sporozoite antigens has been developed at the experimental level mainly for persons with AIDS or with other immunodeficiencies; however, these preparations of antibodies have shown only a limited degree of efficacy both in animals and humans.