The aims of this study were to assess the possible role of peripheral benzodiazepine receptors (pBZrs)¹ in mediating the in vitro effects of carbamazepine (CBZ) on some neutrophil functions in healthy volunteers and to investigate neutrophil function and pBZr expression in patients with epilepsia on CBZ monotherapy for at least 1 year. In vitro CBZ (42–168 μM) concentration-dependently inhibited chemotaxis induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP) or lipopolysaccharide (LPS)-activated human serum. CBZ did not affect random migration, phagocytosis index, phagocytosis frequency, NBT reduction frequency, C. albicans lethality index and resting superoxide production. The pBZr antagonist PK 11195 (1 μM, per se ineffective) reversed the inhibitory effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP. The pBZr agonist Ro 5–4864 (10–100 μM) mimicked the effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP and had no effect on the other parameters. Neutrophils from epileptic patients on chronic CBZ monotherapy had impaired FMLP- and serum-induced chemotaxis and enhanced expression of pBZrs on neutrophils. These data strongly suggest an involvement of pBZrs in mediating the in vitro effects of CBZ on chemotaxis; furthermore, impairment of the same neutrophil function parameters and overexpression of pBZrs in patients are consistent with the hypothesis of an in vivo interaction of CBZ with pBZrs.

Background: The 2011 Very Early Diagnosis of Systemic Sclerosis (VEDOSS) criteria include both patients at risk of progression and those with mild non-progressive forms of SSc. Early diastolic and systolic dysfunction can indicate myocardial fibrosis in SSc patients, yet data on myocardial impairment in the VEDOSS population are limited. Objectives: This study aimed to identify subclinical echocardiographic changes and predictive markers of cardiac dysfunction in both very early and mild-longstanding forms of VEDOSS. Methods: We conducted a cross-sectional observational study involving 61 patients meeting VEDOSS criteria followed up regularly within our Scleroderma referral center. Patients were categorized as early VEDOSS (e-VEDOSS) or mild-longstanding VEDOSS (ml-VEDOSS) based on disease duration (≥10 years). We analyzed clinical and demographic data, focusing on echocardiographic parameters such as the E/A ratio and left ventricular (LV) thickness. Statistical analyses included chi-square, Fischer exact, and student’s t tests, with a significance threshold of p < 0.05. Results: ml-VEDOSS patients were older and reported a higher burden of comorbidities. Autoantibody-positive patients exhibited lower E/A ratios and increased left atrial size. Late nailfold videocapillaroscopic pattern patients exhibited increased PWED thickening and aortic valve insufficiency. Notably, patients undergoing vasodilators experienced larger right atrial volume, while patients receiving Renin-Angiotensin-Aldosterone System (RAAS) inhibitors reported reduced E/A ratio. Multivariable analysis confirmed DLCO% as the sole predictor of both diastolic and systolic impairment in VEDOSS population. Conclusions: Careful monitoring of cardiac function in VEDOSS patients is crucial as subclinical alterations may occur even in the absence of symptoms. DLCO% emerged as an important predictor of LV diastolic dysfunction.