Treatment of uveitis with recombinant human interleukin-13

AIM: To evaluate the anti-inflammatory cytokine interleukin-13 (IL-13) for the treatment of uveitis. METHODS: Uveitis was induced in monkeys by immunisation with human retinal S-antigen. Starting at the onset of disease, the animals were treated with IL-13 at 25 micrograms/kg, or vehicle control, injected subcutaneously once a day for 28 days. Intraocular inflammation was scored by indirect ophthalmoscopy for a period of 56 days. Circulating leucocyte levels were monitored. RESULTS: Uveitis started unilaterally in all but one animal. IL-13 inhibited inflammation both in the eyes in which the disease was present when the treatment was initiated (p = 0.0001), and in the contralateral initially negative eyes (p = 0.0001). After cessation of therapy, there was a progressive increase of inflammation in the IL-13 treated group. However, the beneficial effect of IL-13 extended into the 4 week follow up period. IL-13 produced an increase in circulating polymorphonuclear neutrophils and a decrease in lymphocytes. CONCLUSION: Administration of IL-13 appears to be a promising modality of treatment for severe uveitis.     

Ruminal degradation of tannin‐treated legume meals

The inefficiency of protein utilisation by ruminants fed protein concentrates (based on legume meals) causes serious economic loss and environmental damage owing to their rapid hydrolysis and deamination in the rumen. Thus efforts aimed at slowing the ruminal fermentation of such feeds are needed, and recent studies have observed potentially positive effects of tannins on ruminant nutrition under certain circumstances. Tannins are a complex group of naturally occurring plant polyphenols characterised by their ability to bind with proteins. This property of tannins is considered responsible for the decreased ruminal digestibility of forages both in vivo and in vitro. Under that perspective, commercial tannic acid was added at three proportions (10, 25 and 50 g kg^?1 on a dry matter basis) to four different legume meals (horse bean, kidney bean, soybean and pea), and the effect on in situ dry matter and crude protein ruminal disappearance was assessed. The results confirmed the dose‐dependent (although not persistent after 48 h) slowing of in situ digestibility, this effect being significant at the highest tannin treatment when compared with untreated samples. Scanning electron microscopy revealed that soybean seed endosperm cell walls were protected from digestion by the ruminal microbiota, while the digestion of starch granules was relatively unaffected by tannic acid. Electrophoresis of the protein fractions confirmed the lower digestibility of tannin‐treated seeds as well as the relative lack of alteration of the electrophoretic profile of individual proteins. Implications for the digestion of concentrates in ruminants are discussed. Copyright © 2004 Society of Chemical Industry     

Prevalence and growth characteristics of malignant stem cells in B-lineage acute lymphoblastic leukemia

We used a stroma-supported culture method to study the prevalence and growth characteristics of malignant stem cells in acute lymphoblastic leukemia (ALL). In 51 of 108 B-lineage ALL samples, bone marrow-derived stroma not only inhibited apoptosis of ALL cells but also supported their proliferation in serum-free medium. When single leukemic cells were placed in the stroma-coated wells of microtiter plates, the percentage of wells with leukemic cell growth after 2 to 5 months of culture ranged from 6% to 20% (median, 15%; 5 experiments). The immunophenotypes and genetic features of cells recovered from these cultures were identical to those noted before culture. All cells maintained their stroma dependency and self-renewal capacity. Leukemic clones derived from single cells contained approximately 10(3) to 10(6) cells after 1 month of culture; other clones became detectable only after prolonged culture. Cell growth in stroma-coated wells correlated with the number of initially seeded cells (1 or 10; r = .87). However, the observed percentages of positive wells seeded with 10 cells always exceeded values predicted from results with single-cell-initiated cultures (P < .003 by paired t-test), suggesting stimulation of leukemic cell growth by paracrine factors. In conclusion, the proportion of ALL cells with clonogenic potential may be considerably higher than previously thought.     

Infection and superior vena cava syndrome after pacemaker implantations: major consequences of a minor intervention

Two men, aged 71 and 56 years, with pacemakers, developed the superior vena cava syndrome one and five years, respectively, after infection of the pacemaker pocket. They had been treated with antibiotics and partial removal of the foreign bodies. The conditions of both included occlusion of the superior vena cava and of both subclavian veins. The symptoms disappeared after removal of the total pacemaker system and venous reconstruction. The possibility of a superior vena cava syndrome occurring is increased if other complications have occurred previously, particularly infection. Prevention and treatment comprise on the one hand prevention and treatment of the infection (which is not always obvious) and on the other, earliest possible detection of thromboembolisms.     

Doppler spectrum analysis versus direct femoral artery pressure measurement for rapid assessment of aortoiliac obstruction

Adequate patient selection is required to limit the clinical workload and improve the cost-effectiveness of noninvasive hemodynamic evaluation of the aortoiliac system. In a prospective blinded fashion the traditional invasive technique of direct femoral artery pressure measurements and the computerized Doppler spectrum analysis of blood flow velocities in the common femoral artery were studied. Both tests for rapid assessment of aortoiliac obstruction were compared with duplex ultrasonographic imaging, using a peak systolic velocity ratio of 2.5 to demonstrate stenoses of 50% or more. In a series of 17 consecutive patients (34 aortoiliac segments) with suspected aortoiliac obstructive disease, a good level of agreement (kappa = 0.6) was found for both methods when compared with duplex scanning. Analysis of deviations from the duplex registrations indicated an overestimation of the pathologic cases using femoral artery pressure measurements and an underestimation using Doppler spectrum analysis of blood flow velocities in the common femoral artery. Both methods were well tolerated, but femoral artery pressure measurements had a higher technical failure rate. Because of its noninvasive character and its feasibility the Doppler technique is preferred for the selection of patients for more extensive duplex sonographic investigation.     

The hepatocyte nuclear factor 4 (HNF-4) represses the mitochondrial HMG-CoA synthase gene

Electroconvulsive shock (ECS) activates MAPKs in rat brain and also induces immediate early genes. We investigated whether ECS induces MKP-1, a specific MAPK phosphatase and an immediate early gene, for feedback regulation of MAPK activity. ECS induced MKP-1 in the cortex, but MAPK activity returned to its basal level before MKP-1 protein increased, within 10 min of ECS. MKP-1 protein amount peaked 1 hr after ECS. MKP-1 induced did not lower the basal level of MAPK activity or attenuate MAPK activation by second ECS. MAPK activation in cerebellum was very weak, but the MKP-1 induction was faster and more prominent than in the cortex. These results suggest that ECS induces MKP-1 in various rat brain regions, however, the induction may not be related to the activation of MAPK and the MKP-1 induced may be independent of the regulation of MAPK activity after ECS.     

Factors for progression of periodontal diseases

Tardive dyskinesia is an involuntary movement disorder developing following treatment with neuroleptics. As many as 50% of chronic psychotic patients develop this disabling condition. No treatment has been found effective for tardive dyskinesia. This study was undertaken to meta-analyze the effects of vitamin E (alpha-tocopherol) reported in the last decade. All studies published since 1987, focusing on vitamin E and tardive dyskinesia are reviewed. Double-blind studies are analyzed using measures of effect and variance as described by secondary analysis of magnitude of effects in pooled data. A total of 223 patients received vitamin E treatment (400-1600 IU/day) for tardive dyskinesia, in 12 studies. A significant subgroup (28.3%) showed a modest improvement. Vitamin E was well tolerated, and only rarely did side effects occur-of no clinical significance. Vitamin E is a safe, well-tolerated compound that may provide some beneficial effects in patients suffering from neuroleptic-induced tardive dyskinesia.     

Fixation of facial and auricular prosthesis with osseous implants in cranial bone

OBJECTIVE: To evaluate the use of osseointegrated implants to fix facial and auricular prostheses. DESIGN: Retrospective. SETTING: University Hospital Groningen, the Netherlands. METHODS: Thirty patients were treated with Br?nemark implants for fixation of auricular (21 patients) and orbital (9 patients) prostheses during May 1988-December 1995. The complications during the procedure, the success rate of the implants, skin reactions around the implants and patient satisfaction were recorded. RESULTS: A total of 97 implants were placed. One implant had to be removed after the healing period because it was loose. No other implants were lost during the follow-up period (mean 36 months; range: 12-91). The skin around the implants sometimes showed a mild reaction which could be adequately treated. In most of the cases no inflammation of the skin was observed. Retention, ease of handling and wearing comfort of the facial prostheses were excellent. CONCLUSION: Fixation of facial and auricular prostheses can be improved by osseointegrated implants resulting in high patient satisfaction.     

Short-term and long-term cytokine release by mouse bone marrow mast cells and the differentiated KU-812 cell line are inhibited by brefeldin A

Mast cells and basophils produce a wide range of cytokines, including large amounts of both IL-6 and granulocyte-macrophage CSF (GM-CSF). However, the route by which cytokines are secreted is poorly understood. In the current study, we used two inhibitors of vesicular transport, brefeldin A and monensin, to examine the routes of secretion of IL-6 and GM-CSF in the differentiated KU812 human cell line and cultured mouse bone marrow mast cells (mBMMC). Studies of cytokine production over 6 to 24 h demonstrated that IL-6 and GM-CSF release from both cell types were inhibited by brefeldin A (BFA) following activation with calcium ionophore, A23187. Monensin had similar inhibitory effects to that of BFA on the initial and ongoing IL-6 release from KU812 cells. In contrast, the amount of each cytokine remaining within the cells was significantly enhanced. Similar results were obtained following IgE-mediated activation of mBMMC. BFA significantly inhibited both the constitutive secretion of IL-6 and the immediate ionophore-induced increase in IL-6 release from KU812 cells at 20 min postactivation. However, treatment with these agents did not alter the release of histamine and beta-hexaminidase from either mBMMC or KU812 cells. These studies suggest that both the initial 20-min release of IL-6 and secretion of IL-6 and GM-CSF over up to 24 h by mBMMC and differentiated KU-812 cells occur predominately through a vesicular transport-dependent mechanism, and that little, if any, IL-6 and GM-CSF is released through degranulation.