A reactive oxygen species-generating, cyclooxygenase-2 inhibiting, cancer stem cell-potent tetranuclear copper(ii) cluster.

Tetranuclear copper(ii) complexes containing multiple diclofenac and Schiff base moieties, 1-4, are shown to kill bulk cancer cells and cancer stem cells (CSCs) with low micromolar potency. The most effective complex, 1, elicits its cytotoxic effect by elevating the intracellular reactive oxygen species (ROS) levels and inhibiting cyclooxygenase-2 (COX-2) expression.

Effect of naftifine on neutrophil adhesion.

Effective methods of fungal treatment involve reduction in fungal infections and host inflammatory responses. Naftifine (NF), a topical antifungal agent, is highly active in vitro and in vivo against a wide range of pathogenic fungi. Additionally NF has been shown to inhibit polymorphonuclear leukocyte (PMN) chemotaxis and respiratory burst activity in an irreversible dose-dependent and time-dependent manner. Since leukocyte adherence to endothelia is believed to be one of the initial crucial events in the recruitment of circulating leukocytes to the site of inflammation, we have investigated the in vitro effect of NF on PMN adherence to nylon fiber, BSA-coated glass chamber or polystyrene, and endothelial monolayers via three adherence assays. All three assays demonstrated a statistically significant reduction (p < 0.01-0.001) in PMN adherence to the respective media. In particular, NF (at 30-60 micrograms/ml) significantly inhibited PMN adherence to endothelial monolayers (p < 0.01) as measured spectrophotometrically by the uptake of rose bengal stain. Therefore, NF inhibits PMN adherence to endothelia in our in vitro model system. This inhibition may constitute part of the anti-inflammatory effect of NF.

Modification of neutrophil functions by naftifine.

Naftifine (NF), a topical antimycotic agent, is highly active in vitro and in vivo against a wide range of pathogenic fungi. NF inhibits human polymorphonuclear leucocyte (PMN) chemotaxis. Following stimulation with zymosan-activated serum, 85-97% of the PMNs exhibited detectable membrane ruffling and polarity. In contrast, NF-treated PMNs did not exhibit such chemotactic factor-induced shape changes. We also analysed the effect of NF on PMN superoxide anion (O2-) and chemiluminescence (CL) production, as a measure of respiratory burst activity. Stimulation of PMNs pre-incubated with NF (37 degrees C for 30 min at 1-150 micrograms/ml) by FMLP, PMA and zymosan resulted in a dose-dependent inhibition in PMN CL. Doses of NF which depressed chemotaxis, inhibited CL and diminished O2- production in a statistically significant manner (P < 0.05-0.001). In conclusion, NF alters membrane-related responses in PMNs, and this alteration may be associated with a change in PMN morphology. Binding of NF to PMN membrane sterol, with a subsequent alteration in membrane configuration, is the most likely cause of the inhibition of PMN function. The data collectively document biochemical and morphological differences between control and NF-treated PMNs as determined by stimulus-specific CL and O2- generation and membrane shape change. Such differences may account, in part, for its efficacy in inflammatory fungal skin diseases.

In vitro effect of isotretinoin on monocyte chemotaxis.

The effect of isotretinoin on the chemotaxis of human monocytes was studied in an in vitro system using a Nucleopore chamber. The chemoattractant used was zymosan-activated serum. Inhibition of monocyte chemotaxis was achieved with isotretinoin in concentrations of 1 X 10(-3) M and 5 X 10(-4) M. It is felt that the improvement seen in patients with inflammatory skin diseases such as cystic acne and acne conglobata who are treated with isotretinoin may in part be a result of this anti-inflammatory action.

The effect of Chlamydia trachomatis on luminol-dependent chemiluminescence of human polymorphonuclear leukocytes: requirements for opsonization.

The factors involved in the in vitro interaction of two strains of Chlamydia trachomatis with polymorphonuclear leukocytes were studied by employing the technique of luminol-dependent chemiluminescence. Unopsonized, partially purified elementary bodies of chlamydia failed to induce a significant chemiluminescence response when compared with serum-activated zymosan (less than 90%). Opsonization of the chlamydia with human sera greatly enhanced the chemiluminescence response. This enhancement was independent of the presence or absence of antibody specific for chlamydia or of complement. Primate serum had 77% of the activity of human serum; nonprimate sera (sheep, cow, horse, and rabbit) demonstrated substantially less activity. The magnitude of the chemiluminescence response observed with opsonized chlamydia was also dependent on the chlamydia-to-polymorphonuclear leukocyte ratio, with the greatest effect seen at 10:1. Chlamydia opsonized with human sera containing less than 100 mg of IgG/dl did not stimulate chemiluminescence more than did unopsonized chlamydia. These results suggest that human IgG may interact with C. trachomatis independent of specific antibody-binding sites.

Neutrophil chemotaxis by Propionibacterium acnes lipase and its inhibition.

The chemoattraction of Propionibacterium acnes lipase for neutrophils and the effect of lipase inhibitor and two antibiotic agents on the chemotaxis were evaluated. Of the various fractions tested, partially purified lipase (fraction 2c) was the most active cytotaxin produced by P. acnes. Serum mediators were not required for the generation of chemotaxis by lipase in vitro. Diisopropyl phosphofluoridate at low concentration (10(-4) mM) completely inhibited lipase activity as well as polymorphonuclear leukocyte chemotaxis generated by lipase. Tetracycline hydrochloride and erythromycin base at concentrations of 10(-1) mM and 1 mM, respectively, caused 100% inhibition of PMN migration toward lipase or zymosan-activated serum. The inhibiting activity of the antibiotics was directed against cells independently of any effect on lipase. Chemotaxis by P. acnes lipase suggests a wider role for this enzyme in the inflammatory process and the pathogenesis of acne vulgaris.

Fibroblast nitroblue tetrazolium test and the in-utero diagnosis of chronic granulomatous disease.

A quantitative nitroblue tetrazolium (NBT) test was devised to measure dye reduction by fibroblasts. Statistically significant differences were found between NBT reduction by normal skin and amniotic fibroblasts and by skin fibroblasts of male patients with chronic granulomatous disease (CGD) and their carrier relatives. Cultured amniotic cells may therefore be useful in the prenatal diagnosis of X-linked CGD.

Neutrophil chemotaxis in patients with burns.

In a group of 22 patients with second and third degree burns, seven were found to have impaired chemotaxis. The chemotactic defect was present from two to 68 days and eventually became normal. The impairment was found to be due to a primary transient defect in polymorphonuclear leukocytes and not to an inhibitor or inactivator in the serum.

Diabetes and neutrophil chemotaxis.

The chemotaxis of PMN cells from adult and juvenile diabetics and proper control subjects was found to be comparable. Similarly, chemotactic activity generated from diabetic sera was not different from the activity generated from the normal sera.