Filterability of subpopulations of leukocytes: effect of pentoxifylline

Human leukocytes were separated by density into two fractions, one containing predominantly granulocytes (FI) and the other, lymphocytes and monocytes (FII). The filterability of these fractions and their mixture was determined from the pressure measured during constant flow through 5-microns Nuclepore filters. The pressure-time curve of FI indicates the behavior of a relatively homogeneous cell population. The FII pressure-time curve can be analyzed to distinguish the effect of the more numerous and more filterable lymphocytes from that of the sparser but less filterable monocytes. Pressure generated by mixed leukocytes, which had been treated with 1 and 10 mmol/L of pentoxifylline (PTX) or its metabolite I, was substantially less than untreated control; at 10 mmol/L, the pressure was reduced to about 50% of control. PTX appears to affect the filterability of monocytes and polymorphonuclear leukocytes but not lymphocytes. Scanning electron microscopy showed an inhibition of protopod formation in the treated granulocytes. The degree of cell adhesion to the filter, as measured by the number of cells remaining on the outflow side of the filter, was similar in all groups (FI and FII, treated and untreated). The results indicate that the variations in filterability between the leukocyte subpopulations and the improvement by PTX treatment reflect differences in the cells' ability to deform under the test conditions.     

Relation of human neutrophil phorbol ester receptor occupancy and NADPH- oxidase activity

Phorbol esters are potent stimulants of the respiratory burst of the human neutrophil as assessed by superoxide (O2-) generation in whole cells and by NADPH-oxidase activity in a broken-cell 27,000-g particulate fraction. Phorbol 12-myristate, 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDBu) stimulate production of O2- by human neutrophils with ED50 concentrations of 3.9 +/- 2.1 and 41.7 +/- 7.1 nM, respectively. The relation of biologic activity to receptor occupancy was assessed with binding studies of PMA and PDBu. Phorbol ester binding revealed a single high affinity phorbol ester receptor present at 7.6 x 10(5) sites/cell. The binding affinities for PMA and PDBu, 4.9 nM and 38.4 nM, respectively, agreed quantitatively with that of biologic potencies. Because of the high concentration of phorbol ester receptors (up to 125 nM) and the large amount of nonspecific binding at high cell density, apparent discrepancies between ED50's for NADPH-oxidase and whole cell O2- generation were noted. With the use of low cell concentrations, quantitative agreement between intact cell production of O2-, NADPH-oxidase activity, and receptor binding was found. These results further support the identity of the NADPH-oxidase as the enzymatic source of respiratory burst O2- production in human neutrophils.     

Systemic use of non‐biologic agents in orofacial diseases: other immunomodulatory agents

Systemic non‐biologic agents have long been in clinical use in medicine – often with considerable efficacy, albeit with some adverse effects – as with all medications. With the advent of biologic agents, all of which currently are restricted to systemic use, there is a growing need to ensure which agents have the better therapeutic ratio. The non‐biologic agents (NBAs) include a range of agents, most importantly the corticosteroids (steroids). Previous articles by us in this series have discussed systemic use of corticosteroids and purine synthesis inhibitors; the other immunomodulating agents (calcineurin inhibitors, thalidomide, dapsone, colchicine and cyclophosphamide) are reviewed in this final article.     

Oral lichenoid lesions of the upper lip and gingiva: What we know so far

The clinical presentation of oral lichen planus and oral lichenoid lesions is diverse. A special category of patients presents with lichenoid lesions affecting only the mucosa of their upper lip and the anterior upper gingiva. This is a concise review summarizing the specific characteristics of these patients.     

Successful medication withdrawal after cognitive‐behavioral therapy in a treatment‐resistant preadolescent male with obsessive‐compulsive disorder

There are no reports of a child taking a selective serotonin reuptake inhibitor and an atypical anti‐psychotic being successfully tapered from these medications after completion of cognitive‐behavioral therapy (CBT) for obsessive‐compulsive disorder. With this in mind, we report the case of an 8.5‐year–old male who was taking risperidone 0.5 mg bid, sertraline 100 mg, and atomoxetine 25 mg at presentation. After a successful course of CBT, we describe how medications were systematically withdrawn. Implications of this case on practice parameters (e.g., CBT may be an effective augmenting agent for those non‐responsive to initial pharmacological treatments) are highlighted. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.     

Multiple sclerosis: In situ evidence for antibody- and complement-mediated demyelination

We describe a case of multiple sclerosis characterized by deposition of immunoglobulin and complement in the areas of active demyelination. This was particularly evident for the C9neo antigen, which is a marker for the activated lytic complement complex and was exclusively deposited in the areas of active myelin destruction. In addition, macrophages in the lesions contained degradation products that were immunoreactive for myelin antigens, immunoglobulins, and C9neo antigen. Destruction of myelin sheaths was associated with incomplete loss of oligodendrocytes in the active areas and reappearance of oligodendrocytes with remyelination in the inactive plaque center.