Iron is a regulatory component of human IL-1beta production. Support for regional variability in the lung.

The human lung accumulates iron with senescence. Smoking escalates the accumulation of iron, and we have demonstrated regional variability in the accumulation of iron in smokers' lungs. Iron has been reported to influence the production of a number of proinflammatory mediators, including human interleukin (IL)-1beta. We postulated that we could (1) demonstrate regional differences in the release of IL-1beta from human alveolar macrophages and (2) influence the production of IL-1beta in human macrophages by altering intracellular iron concentrations. To test these hypotheses, alveolar macrophages were obtained by independent lavage of the upper and lower lobes of healthy volunteers (both smokers and nonsmokers), after which the ability of each population to secrete IL-1beta was quantified, together with their ability to produce tumor necrosis factor-alpha, IL-6, and IL-8. Additionally, we established an in vitro model of "iron-loaded" cells of the human myelomonocytic cell line THP-1 in order to examine more directly the effect of iron and its chelation on the secretion of IL-1beta. We report here that an intracellular, chelatable pool of iron expands with exogenous iron-loading as well as with lipopolysaccharide (LPS) stimulation and appears to suppress transcription of IL-1beta, whereas shrinkage of this pool by early chelation augments transcription of IL-1beta beyond that induced by LPS alone. And finally, we demonstrate a regional relationship in the lung between excess alveolar iron and the production of human alveolar macrophage-derived IL-1beta, suggesting a partnership between iron and inflammation that may have clinical significance, especially in relation to lung diseases with a regional predominance.

Differential regulation of human alveolar macrophage-derived interleukin-1beta and tumor necrosis factor-alpha by iron.

Human lungs accumulate iron with the aging process. In some circumstances associated with lung injury (eg, smoking), this acquisition of iron in lung tissue and alveolar macrophages (AMs) is escalated. We hypothesized that excess cellular iron interfered with the production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1-beta) by AMs. To examine this hypothesis, we acquired AMs from smokers and nonsmokers by bronchoalveolar lavage. AMs were stimulated by lipopolysaccharide (LPS), with and without deferoxamine (DFA), a chelator of iron. Enzyme-linked immunosorbent assay and Northern analysis were used to quantitate cytokine concentrations and mRNA. The addition of DFA increased the release of IL-1-beta, but not TNF-alpha, from AMs from smokers and nonsmokers. The DFA augmentation of LPS-induced IL-1-beta was more pronounced in smokers' AMs than in those from non-smokers (4.5-fold vs 2.6-fold increase). The addition of FeCl3 to DFA diminished the augmenting effect on the release of IL-1-beta, suggesting that the mechanism of action involved iron chelation. Conversely, as the intensity of iron chelation increased, the release of IL-1-beta and TNF-alpha decreased, as was also shown with hydroxyl radical scavenging by dimethylthiourea. This inhibition, however, occurred at very different thresholds for each cytokine. These data support a relationship between excess alveolar iron and the generation of inflammation within the lung.

Corneal penetration of diclofenac from a fixed combination of diclofenac-gentamicin eyedrops.

PURPOSE: To establish the corneal penetration of diclofenac in the presence of gentamicin in patients having cataract surgery. SETTING: Kantonsspital Augenklinik, Aarau, and Hôpital Jules Gonin, Lausanne, Switzerland. METHODS: Eligible patients having cataract surgery (39 women, 30 men) were treated with 4 drops of diclofenac 0.1%-gentamicin 0.3% (Voltamicin) instilled at 20 minute intervals. Paracentesis was performed 15, 30, or 60 minutes after the last instillation, and a sample of aqueous humor was collected for analysis of diclofenac by high-performance liquid chromatography. Blood samples of some patients were obtained before surgery for analysis. RESULTS: Mean diclofenac levels (+/- SD) in the aqueous humor 15, 30, and 60 minutes after the last instillation were 72 +/- 84, 108 +/- 87, and 201 +/- 116 ng/mL (= 682 nMol/L), respectively. Diclofenac remained below the limit of detection (5 ng/mL) in all samples of blood serum. In general, local tolerance was good; no side effects were reported. Comparison of the data with published results of topically instilled diclofenac 0.1% suggests that the concentration of diclofenac in the aqueous humor achieved with 4 instillations of the combination product is similar to that achieved with 8 instillations of diclofenac 0.1% (Voltaren Ophtha) alone. CONCLUSIONS: Drug levels of diclofenac in the aqueous humor well above IC-50 for cyclo-oxygenase were achieved with the regimen applied. No inhibitory effect by the gentamicin or vehicle was observed. Comparison of these data with published results of Voltaren Ophtha implies a 2-fold better penetration of diclofenac with the diclofenac-gentamicin combination.

[Acute amaurosis in EPH gestosis]. / Akute Amaurose bei EPH-Gestose.

For more than one hundred years ophthalmologists have been interested in the occurrence of acute blindness in patients with toxemia of pregnancy. In addition to general symptoms of toxemia of pregnancy there are specific symptoms and findings in the visual and cortical pathways. Acute blindness during toxemias of pregnancy can be divided into transient-ocular or cortical, as well as permanent, mostly of ocular origin. There are diverse causes of this pathological condition.

Comparison of the anti-inflammatory potency and local tolerance of diclofenac and indomethacin eye drops in the postoperative management of patients undergoing ECCE with PCL.

Prostaglandins have been shown to mediate various manifestations of ocular inflammation. Diclofenac and indomethacin are thought to inhibit cyclooxygenase, an enzyme necessary for prostaglandin biosynthesis. The anti-inflammatory effect and subjective tolerance of topical diclofenac 0.1% and indomethacin 0.1% were examined in the postoperative treatment of 64 patients undergoing extracapsular cataract surgery with IOL implantation in a prospective, comparative, single masked study. Patients with preexisting ocular disease or whose intraoperative course was complicated were excluded from the study. Ophthalmologic examinations were performed preoperatively and at days: 1, 4-6, and 28-30 post surgery. Tolerance was assessed by subjective patient evaluation. There was no significant difference (p < 0.05) in postoperative inflammation among the two treatment groups. There was a trend for more severe corneal edema on day 4-6 in the indomethacin group. Diclofenac was slightly better tolerated.

Examination of Koch's postulates for Borrelia burgdorferi as the causative agent of limb/joint dysfunction in dogs with borreliosis.

Borrelia burgdorferi has been implicated as the causative agent of borreliosis in dogs, which is characteristically a limb/joint disorder, but can be associated with multiple-organ dysfunction. Attempts to reproduce this disease by inoculating dogs with B burgdorferi have not been successful. In the study of this report, B burgdorferi from Ixodes dammini ticks was used to induce signs of limb/joint dysfunction, fever, anorexia, depression, and systemic infection in dogs. A pure culture of this bacterium from the blood of an infected dog has been used to fulfill Koch's postulates for B burgdorferi as the causative agent of limb/joint dysfunction associated with borreliosis in dogs.

Immunogenicity and efficacy study of a commercial Borrelia burgdorferi bacterin.

The immunogenicity and efficacy of a commercial Borrelia burgdorferi bacterin was evaluated for stimulation of the host immune response and protection against clinical disease associated with experimentally induced borreliosis in dogs. A total of 30 vaccinated and 24 control dogs were used in 3 separate studies. The vaccine was given IM as two 1-ml doses separated by a 3-week interval. Two weeks or 5 months following the last vaccination, the dogs were challenge inoculated with 7 daily doses of a virulent preparation of a B burgdorferi field isolate through intraperitoneal, subcutaneous, and intradermal routes with or without glucocorticoid administration at the same time. The development of B burgdorferi spirochetemia and clinical disease in the dogs after challenge exposure was studied. Serum samples were obtained from the dogs at various times during the study for serum neutralizing antibody determination and protein immunoblot antibody assay against various geographic isolates of B burgdorferi. Challenge exposure induced limb/joint disorder, fever, anorexia, signs of depression, and B burgdorferi spirochetemia in the nonvaccinated control dogs. The vaccine was found to elicit cross-reactive serum neutralizing and protein immunoblot antibody responses in dogs to various isolates of B burgdorferi and to protect the vaccinated dogs against experimentally induced borreliosis.

[Pseudotumor cerebri, clinical parameters and therapeutic modalities]. / Pseudotumor cerebri, Verlaufsparameter und Therapiemodalitäten.

Pseudotumor cerebri is a central nervous disorder with elevated intracranial pressure that is most common among young obese women. It presents with headache, transient visual obscurations and loss of central vision. Papilledema and visual field defects are frequent. Acetazolamid can be used for treatment. If medical treatment is not successful, optic nerve sheath decompression is recommended. Three patients were treated medically and there were treated surgically. Both methods stabilized or improved visual fields and central vision.

[The Molteno implant in intractable glaucoma]. / Das Molteno-Implant beim nicht mehr beherrschbaren Glaukom.

The results of a study with Molteno-implants in eyes with intractable glaucoma, performed for the first time in Switzerland, are presented and discussed with regard to visual acuity, intraocular pressure, and painlessness.

[The tearing eye in newborn infants and young children: good results with short-term conservative therapy]. / Das tränende Auge beim Neugeborenen und Kleinkind: Gute Ergebnisse mit einer kurzdauernden konservativen Therapie.

In this article the authors communicate the results of a short-term conservative treatment for lacrimation in infants with presumed dacryostenosis. The results so far are encouraging and in most cases enable probing of the lacrimal duct to be dispensed with. If the patient fails to respond to the treatment the delay thus caused until probing can be performed is only brief.