Serum Factors Causing Impaired Macrophage Function in Systemic Lupus Erythematosus

Leukocytes from patients with systemic lupus erythematosus (SLE) and healthy controls were cultured for 4 days in either SLE serum or control serum The remaining monolayer of monocyte-derived macrophages was allowed to ingest yeast cells. Macrophages (from SLE patients or controls) incubated in SLE sera presented impaired phagocytic activity and glass adherence compared with cells grown in control sera SLE sera contain one or more factors that impair macrophage function; IgG-containing immune complexes may be one such factor.     

Effect of a new inhibitor of lipid peroxidation on kidney function after ischaemia-reperfusion. A study on rat and rabbit kidneys

Lipid peroxidation of mitochondrial and cell membrane structures is the final step in the oxygen radical-induced damage observed at reperfusion of kidneys after ischaemia. We compared the ability of an indeno-indol compound (code name H290/51) with that of α-tocopherol to inhibit lipid peroxidation in reoxygenated isolated rat renal tissue in vitro measured as production of TBARS (thiobarbituric acid reactive substances). H290/51 was 100 times more efficient than α-tocopherol. Treatment of rats in vivo with H290/51 in a dosage giving a plasma concentration of 500 nmol L^-1 inhibited TBARS production measured in vitro by 80%. Treatment of rabbits with H290/51 almost completely inhibited radical production at reperfusion after 60 min of ischaemia measured with spin trap technique using OXANOH (2-ethyl-3-hydroxy-2,4,4-trimethyloxazolidine) as a spin trap. Furthermore, such pretreatment significantly improved kidney function and survival of rabbits subjected to 60 min of ischaemia to the left kidney and contralateral nephrectomy. These studies stress the importance of inhibiting lipid peroxidation to prevent the ischaemia-reperfusion damage and furthermore suggest a role for treatment with antioxidants like H290/51 in clinical practice, e.g. at reconstructive renal surgery and transplantation.     

Growth resistance-sized arteries in response to bladder hypertrophy in the rat: time-course,DNA-synthesis and LDH-isoform pattern

Bladder growth was induced by partial urethral obstruction. Bladder hypertrophy was evident at 53 h after obstruction and continued over a 6 weeks period. Small bladder arteries were taken from fixed anatomical locations of the bladder circulation, mounted in a small vessel myograph and the optimal diameter for maximal isometric force development was determined (L_max, K⁺=125 mm stimulation). Bladder hypertrophy was associated with an enlarged L_max from 53 h onward (compared with sham-operated controls) and L_max continued to increase until 10 days after urethral obstruction. Between 10 days and 6 weeks no further increase of the diameter was observed. Increased diameters in vitro were accompanied by a transiently increased [³H]Thymidine uptake in the small arteries which peaked at 53 h after obstruction but was still above background at 10 days. At this time point, small arterial growth was associated with a significant relative increase in the M isoform of LDH as determined with agarose electrophoresis on tissue homogenates. Thus organ growth induced small vessel growth in the rat is characterized by a rapid onset, increased but transient DNA-turnover and LDH-isoform changes. The latter mimic changes seen in other types of smooth muscle growth.     

Eosinophils, secretory responsiveness and glucocorticoid-induced effects on the nasal mucosa during a weak pollen season

This study examined the seasonal effects on eosinophils and secretory responsiveness of the nasal mucosa in 22 patients with allergic rhinitis due to birch pollen (11 patients received placebo and 11 budesonide, 200 micrograms once daily in each nostril). The pollen counts during the study season were too low to produce a significant symptomatology. Hence, our findings demonstrate threshold alterations of the airway mucosa in allergic rhinitis and their inhibition by anti-inflammatory drug intervention. The patients were monitored for 8 weeks with daily recordings of pollen counts and symptom scores. Once every week a series of laboratory tests was carried out: the local eosinophil influx was determined using a Rhinobrush technique; the levels of eosinophil cationic protein (ECP) were analysed in nasal lavage fluids; and the secretory response to intranasal methacholine was measured. Treatments started after a 2-week run-in period. The proportion of eosinophils increased markedly in the placebo group and was elevated also during the last two study weeks when the pollen counts were practically nil. The secretory responsiveness to methacholine increased during the pollen season and returned to baseline towards the end of the study period. The topical glucocorticoid treatment reduced the proportion of eosinophils, the ECP levels, and the secretory response to methacholine compared to placebo. We conclude that the increased traffic and activity of eosinophils and less conspicuously the increased secretory responsiveness are expressions of the mucosal inflammation that precede the development of symptoms in seasonal allergic rhinitis.     

Toxicokinetics of Nickel in Mice Studied with the {gamma}-Emitting Isotope 57Ni

The -emitting isotope ⁵⁷Ni was generated in a cyclotron to allowwhole-body counting of laboratory animals dosed with nickel.⁵⁷NiCl₂ was administered either orally by gastric intubationor by intraperitoneal injection to groups of mice in doses equivalentto the average human daily dietary nickel intake per mass unit.When given orally, the whole-body retention (WBR) was 0.02–0.36%of the administered dose at 45–75 hr. When given intraperitoneally,the WBR was 1–6% at 20–50 hr. After adjustment forthe rapid excretion of systemic nickel, the intestinal absorptioncould be estimated to be 1.7–10%. The relative WBR didnot vary with the magnitude of the dose within 0.05–5µmol Ni/kg given orally or 0.005–0.5 µmol/kggiven intraperitoneally. At 8 hr, the tissue concentration washighest in the kidneys, followed by the carcass, lungs, testicles,liver, and the spleen. After 20 hr, the highest concentrationswere still found in the kidneys followed by the lungs, the liver,and the carcass. At 20 hr after oral administration, 50–70%of ⁵⁷Ni retained in the body was within the carcass. The secondhighest nickel content was found in the kidneys, followed bythe liver and lungs. Whereas nickel in the kidneys was rapidlyexcreted, the elimination from the lungs and liver was relativelyslow, thereby, after 40 hr, resulting in a higher nickel contentin the liver than that in the kidneys. When nickel was givenintraperitoneally, practically no nickel was transported viathe portal vein to the liver after 20 hr, resulting in a lownickel content in the liver and a higher content in the kidney.These results document that the use of ⁵⁷Ni for studies on nickeltoxicokinetics is feasible and useful, and that the method isespecially well suited for comparative studies with a durationof up to 6 days.     

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial

Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation bur absolute success races are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safely and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8–32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO ≤8 ppm.; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.