Our results demonstrate that subjects who developed peripheral neuropathy while staying on treatment with ddl, ddC and d4T had acetyl-carnitine deficiency. The normal levels of total carnitine in the study group appear to indicate the specificity of the defect and rule out coexisting relevant nutritional problems. The critical role of acetyl-carnitine for the metabolism and function of the peripheral nerves supports the view that the acetyl-carnitine deficiency found in these subjects may contribute to the neurotoxicity of ddl, ddC and d4T, even though the interference with mitochondrial DNA synthesis is regarded as the main cause of their toxicity.

Polymorphonuclear leukocytes (PMN), atrial natriuretic peptide (ANP) and leukotriene B4 (LTB4) reportedly play a major role in ischemia/reperfusion states of coronary artery disease. We sought to determine whether ANP and LTB4 cooperate in inducing PMN activation with consequent modulation of membrane molecules required for adherence to endothelium and myocardial cells, namely CD11b and L-selectin and the release of toxic oxygen radicals. ANP (from 10(-16) to 10(-8) M), LTB4 (from 10(-10) to 10(-6) M) and combinations of the two were incubated with normal PMN at 37 degrees C for 15 minutes. Membrane molecules modulation was measured by flow cytometry using specific monoclonal antibodies. Hydrogen peroxide production, an indicator of the capacity of PMN to release toxic oxygen species was quantified by flow cytometry using the peroxide-sensitive fluorescent probe dichlorofluorescein diacetate. ANP, uneffective when used alone, dose-dependently potentiated the PMN response to LTB4 (10(-9) M) as evidenced by an up-regulation of CD11b expression and peroxide production, and a down-regulation of L-selectin expression. These effects were prevented dose-dependently by the protein kinase C (PKC) inhibitor staurosporine (from 10 to 160 microM). Two carnitine congeners, palmytoylcarnitine (tested from 125 pg to 2 micrograms/ml) that also possesses an established ability to antagonise PKC and L-carnitine (tested from 12 to 200 ng/ml) were also effective. These data indicate that ANP potentiates LTB4 in inducing PMN mobilization and activation with a possible consequent detrimental effect on cardiac tissue and evisages the usefulness of PMN metabolism modulators.

Introduction: Hidradenitis suppurativa is a complex, chronic, difficult to treat condition belonging to the spectrum of cutaneous immune-mediated inflammatory diseases. Systemic treatment options for moderate-severe disease are limited to TNF-alpha antagonists and other biologic agents, with limited clinical evidence. Patient concerns: We report two adult patients with severe hidradenitis suppurativa presenting concomitant psoriatic arthritis and multiple medical comorbidities. Both were ineligible or resistant to adalimumab, the only biologic drug approved for the treatment of hidradenitis. Diagnosis: Both patients were diagnosed with severe Hurley III-stage disease and psoriatic arthritis, showing resistance to first-line systemic treatments and a complex comorbidity profile. Interventions: Patients underwent treatment with apremilast, an oral phosphodiesterase-4 inhibitor, approved for the treatment of psoriatic arthritis. Outcomes: After 16 weeks of treatment, a clinically relevant improvement of inflammatory lesions, skin- and arthritis-related pain, and patient-reported outcomes was achieved in both patients. Apremilast was well tolerated and continued up to 48 weeks of treatment. Conclusion: We report the “real-life” use of apremilast in the treatment of multimorbid patients with hidradenitis suppurativa and review its potential role in the management of this severe condition.

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