Influence of nifedipine on plasma membrane fluidity and oxidative burst of polymorphonuclear leucocytes.

It has been demonstrated that the calcium antagonist nifedipine inhibits the reactive oxygen species (ROS) production by polymorphonuclear leucocytes (PMNLs) activated with phorbol myristate acetate (PMA), but the mechanism underlying this effect is still unknown. In the present study we investigated the influence of nifedipine on the PMNL plasma membrane using 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5,hexatriene (TMA-DPH) fluorescence polarization (P) and on PMA- and N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced ROS production, measured by luminol-dependent chemiluminescence (CL). The plasma membrane fluidity of untreated PMNLs, expressed as P, was 0.371 +/- 0.008. After preincubation of 15 min, nifedipine induced a significant change in P values only at a concentration of 10(-4) M (P = 0.00018). After preincubation of 60 min significant changes in P values were also observed at concentrations of 10(-6) M (P = 0.023) and 10(-7) M (P = 0.023). PMA-induced ROS production by PMNLs was markedly inhibited by nifedipine. Nifedipine also determined a striking change in the FMLP-induced CL response, characterized by both an overall inhibition of PMNL activity and a modification of the kinetics of the oxidative burst (rapid increase in ROS production followed by a pronounced drop in the PMNL response). Such a pattern was found at concentrations of 10(-4) M (preincubation time: 15 min), 10(-6) M and 10(-7) M (preincubation time: 60 min). These findings indicate that nifedipine directly interacts with the PMNLs by inducing a marked decrease in plasma membrane fluidity and an inhibition of the oxidative burst.

Acute effects of single dose nifedipine on cold-induced changes of microvascular dynamics in systemic sclerosis.

Calcium-channel blockers are widely used in the treatment of systemic sclerosis (SSc), but their in vivo influence on microcirculation is not fully elucidated. We evaluated the acute effect of nifedipine on the cold-induced changes of microvascular dynamics in SSc. Eleven SSc patients and seven healthy volunteers were studied. Dynamic aspects of the nailfold microcirculation (appearance time at the nailfold, transcapillary diffusion, interstitial distribution and interstitial clearance of sodium fluorescein given i.v.) were quantitatively assessed by a computer-aided fluorescence videomicroscope. Fluorescent light intensities (FLIs) at predefinite pericapillary and interstitial sites were measured under three experimental conditions: (1) baseline; (2) after cold test; (3) after single oral administration of 10 mg of nifedipine 5 min before cold exposure. The interval between the intravenous injection of sodium fluorescein and the first appearance of the dye at the nailfold significantly increased after cold exposure in the SSc patients (224.1 +/- 182.3 s vs 27.5 +/- 25.1 s at baseline) (P = 0.0026), but not in the controls (28.0 +/- 13.3 s vs 29.6 +/- 12.4 s at baseline). The effect of cold exposure on the appearance of the dye was not significantly antagonized by nifedipine (112.7 +/- 91.8 s) in the SSc patients (P = 0.07). Cold exposure significantly decreased transcapillary diffusion and interstitial distribution of sodium fluorescein in the SSc patients (P < 0.016), but not in the controls. The cold-induced changes of FLI values were antagonized by nifedipine in the SSc patients (P < 0.016), but not in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Capillary permeability in fibromyalgia.

OBJECTIVE: To examine capillary permeability in fibromyalgia (FMS) we studied the nailfold capillaries of 13 unselected patients with FMS and 9 healthy controls using dynamic fluorescence videomicroscopy. METHODS: The transcapillary permeability of a 20% solution of sodium fluorescein injected into an antecubital vein was assessed by videodensitometric analysis. The pericapillary and interstitial fluorescent light intensities (FLI) were calculated at different sites on a transverse axis crossing the selected capillary. RESULTS: Fluorescence videomicroscopy revealed no abnormalities in the pattern of dye distribution around the nailfold capillaries in the patient group. Videodensitometric analysis showed a trend to an increased early transcapillary diffusion in patients with FMS, but the difference was only significant at 3 s from the first appearance of the dye (p < 0.05). From 10 s to 1 min after the dye's appearance, the mean FLI in the patients equalled that of the controls. The patients with FMS showed an earlier but lower FLI peak. Moreover, the FLI were significantly lower in the patients than in the controls from 5 to 30 min after the dye appearance in all of the sites of the densitometric analysis (p < 0.05). Thirty min after the first appearance of the dye, the FLI was reduced by more than 50% in the patient group compared to the controls. CONCLUSION: Our results indicate that transcapillary permeability and the interstitial persistence of the tracer in FMS are significantly reduced compared to controls. This difference may be caused by the abnormal microvascular dynamics induced by low capillary flow and/or capillary bed hypotension.

Effects of peripheral cold exposure on microvascular dynamics in systemic sclerosis.

OBJECTIVE: To determine the influence of cold exposure on microvascular permeability in systemic sclerosis (SSc). METHODS: Thirteen patients with SSc were studied by dynamic fluorescence videomicroscopy under basal conditions and after exposure to cold. RESULTS: Exposure to cold caused a significant reduction in the interstitial concentration of sodium fluorescein (P < 0.05 to 0.001). CONCLUSION: Our findings show that cold exposure has a striking effect on microvascular dynamics in SSc.

Raynaud's phenomenon in rheumatoid arthritis.

The prevalence of Raynaud's phenomenon in RA was retrospectively reviewed in 411 consecutive RA patients and in a control group of 919 consecutive outpatients with OA. Raynaud's phenomenon was found in 19 (4.6%) of 411 RA patients and in 52 (5.6%) of 919 patients with OA: its prevalence was 4.3% (13 cases) in RA inpatients and 5.4% (six cases) in RA outpatients. Among the RA patients, the prevalence of Raynaud's phenomenon was 7.5% in men (7% of inpatients, 8.8% of outpatients) and 3.2% in women (3% of inpatients, 3.9% of outpatients) (P = N.S.). Conversely, the prevalence of Raynaud's phenomenon in patients with OA was higher in women (6.5%) than in men (2.9%) (P = 0.045). Our study indicates that the reported association between Raynaud's phenomenon and RA cannot be confirmed on the basis of a retrospective assessment of its prevalence.

Labial capillary microscopy in systemic sclerosis.

OBJECTIVES: To investigate whether in vivo capillary microscopy of the lower lip mucosa can be used to assess microvascular disease in systemic sclerosis. METHODS: Thirteen patients with systemic sclerosis and 11 healthy control subjects were studied by conventional nailfold capillary microscopy and labial capillaroscopy. The following parameters were analysed: loop length; loop width (maximum distance between the arteriolar and venular limbs); loop density (number of capillaries/mm2); venular plexus visibility; megacapillaries; and the architectural arrangement of the capillary network. RESULTS: A typical 'scleroderma pattern' at the nailfold was observed in 12 of 13 (92%) patients with systemic sclerosis. Labial capillaroscopy showed a different morphological pattern of microangiopathy. A diffuse architectural derangement of the capillary network was the most striking abnormality in 12 (92%) patients. Labial capillaries in the patients with systemic sclerosis were shorter (mean (SD) loop length 133 (32.2) microns) than in healthy controls (211 (48.4) microns) and showed an increased loop width (41.7 (13.1) v 27.6 (5.5) microns in controls. The loop density was 10.5 (4.6) capillaries/mm2 in patients with systemic sclerosis and 9 (1.7) capillaries/mm2 in controls. Labial capillaroscopy in patients with systemic sclerosis did not provide definite evidence of enlarged capillaries or avascular areas, or both, even where such abnormalities were clearly evident at the nailfold. CONCLUSIONS: This study shows that labial capillary microscopy is a simple, non-invasive technique which allows a careful morphological assessment of the mucosal microcirculation. Labial capillaroscopy in patients with systemic sclerosis showed significant microvascular changes with respect to the controls. The results of labial and nailfold capillaroscopy are not superimposable, even if some common findings, such as architectural derangement, are present.

Influence of dichloromethylene diphosphonate on reactive oxygen species production by human neutrophils.

Biphosphonates suppress bone destruction in various diseases. Several studies have demonstrated the potential use of biphosphonate in arthritis. The results of these studies indicate that the effectiveness of the biphosphonates, for inhibiting the arthritic process, is related to their antiresorptive properties. It has been shown that the generation of reactive oxygen species is associated with the formation of new osteoclasts and enhanced bone resorption. We studied the effects of the dichloromethylene diphosphonate on the reactive oxygen species production by activated polymorphonuclear leucocytes, measured by chemiluminescence. Our results indicate a dose-dependent inhibitory effect of dichloromethylene diphosphonate on reactive oxygen species production by polymorphonuclear leucocytes stimulated with N-formil-methionyl-leucyl-phenylalanine, the calcium ionophore A23187 and phorbol myristate acetate. The mechanisms by which this biphosphonate inhibits the reactive oxygen species production by activated polymorphonuclear leucocytes are discussed.

Nailfold capillary permeability in psoriatic arthritis.

This study is the first report of the permeability status of nailfold capillaries in psoriatic arthritis (PA). "Traditional" nailfold capillary microscopy and intravital fluorescence videomicroscopy were carried out at the nailfold of 13 patients with PA. Twenty five healthy subjects served as controls for nailfold capillary microscopy, and 15 out of these for fluorescence videomicroscopy. The following parameters were assessed: capillary length, apex width, maximum loop width, maximum limb width, loop density, visibility of subpapillary venular plexus, loop tortuosity, transcapillary diffusion, and interstitial concentration at different sites and times of Na-fluorescein given in intravenous bolus. Morphometric analysis of capillaroscopic findings showed a significant increase of loop length (mean +/- SD: 290.1 +/- 73.5 microns) when compared to healthy controls (223.3 +/- 51.9 microns) (P < 0.02). Transcapillary passage of Na-fluorescein was homogeneous and symmetric both in PA patients and in controls. Mean transcapillary and interstitial diffusion was not significantly enhanced at the nailfold in PA patients. Our data support the view that PA is not characterized by a specific capillaroscopic pattern and/or significant abnormalities of microvascular dynamics at the nailfold.