Giovanna d' Aragona, Duchessa d' Amalfi

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Dermal nerve fibre and mast cell density, and proximity of mast cells to nerve fibres in the skin of patients with complex regional pain syndrome

An interaction between cutaneous nerves and mast cells may contribute to pain in complex regional pain syndrome (CRPS). To explore this, we investigated the density of dermal nerve fibres, and the density and proximity of mast cells to nerve fibres, in skin biopsies obtained from the affected and unaffected limbs of 57 patients with CRPS and 28 site-matched healthy controls. The percentage of the dermis stained by the pan-neuronal marker protein gene-product 9.5 was lower in the affected limb of patients than in controls (0.12 ± 0.01% versus 0.22 ± 0.04%, P \u3c 0.05), indicating a reduction in dermal nerve fibre density. This parameter did not correlate with CRPS duration. However, it was lower in the affected than unaffected limb of patients with warm CRPS. Dermal mast cell numbers were similar in patients and controls, but the percentage of mast cells less than 5 μm from nerve fibres was significantly lower in the affected and unaffected limbs of patients than in controls (16.8 ±1.7%, 16.5 ± 1.7% and 31.4 ± 2.3% respectively, P \u3c 0.05). We confirm previous findings of a mild neuropathy in CRPS. Our findings suggest that this either develops very early after injury or precedes CRPS onset. Loss of dermal nerve fibres in CRPS might result in loss of chemotactic signals, thus halting mast cell migration towards surviving nerve fibres. Failure of normal nerve fibre-mast cell interactions could contribute to the pathophysiology of CRPS

Computer-aided design and manufacturing technology applied to total nasal reconstruction

The principles of nasal reconstruction include the need to reconstruct three tissue layers, the need to restore entire skin aesthetical units, and, possibly, the replacement with like tissues. Computer-aided design (CAD) and computer-aided manu- facturing (CAM) technologies were applied to two total nasal reconstructions in male patients who underwent rhinectomy for cancer. Three-dimensional (3D) data were obtained from computerized tomography (CT) scan-derived DICOM files (Digital Imaging and Communications in Medicine), this allowed us to design the shape of the reconstructive nose in order to mimic the native nose and to plan dimensions and angles. A custom-made titanium plate was manufactured for the struc- ture and a bi-dimensional template for the forehead flap was printed. The patients underwent a total nasal reconstruction in three layers: local flaps for the lining, custom-made titanium plate for the structure, and expanded forehead flap for the skin. Forehead flap pedicle was divided 3 weeks postoperatively under local anesthesia in an outpatient clinic, as well as further minor refinements. The patients underwent a 6-month post-operative CT scan in order to compare the result to the planned nose. No complications were reported. The superimposition demonstrated a 92% match in case 1 and 95% match in case 2 between the reconstructed nose and the planned one. Forehead flap is still the most favorable option for nasal reconstruction, CAD technology allows to implement the planning and makes the procedure easier; moreover, the use of a CAM plate for the structure allows to reconstruct a nose with the desired naso-frontal angle

Improved Reversal Learning and Working Memory and Enhanced Reactivity to Novelty in Mice with Enhanced GABAergic Innervation in the Dentate Gyrus

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Impaired Fear Extinction Due to a Deficit in Ca2+ Influx Through L-Type Voltage-Gated Ca2+ Channels in Mice Deficient for Tenascin-C

Mice deficient in the extracellular matrix glycoprotein tenascin-C (TNC−/−) express a deficit in specific forms of hippocampal synaptic plasticity, which involve the L-type voltage-gated Ca2+ channels (L-VGCCs). The mechanisms underlying this deficit and its functional implications for learning and memory have not been investigated. In line with previous findings, we report on impairment in theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in TNC−/− mice in the CA1 hippocampal region and its rescue by the L-VGCC activator Bay K-8644. We further found that the overall pattern of L-VGCC expression in the hippocampus in TNC−/− mice was normal, but Western blot analysis results uncovered upregulated expression of the Cav1.2 and Cav1.3 α-subunits of L-VGCCs. However, these L-VGCCs were not fully functional in TNC−/− mice, as demonstrated by Ca2+ imaging, which revealed a reduction of nifedipine-sensitive Ca2+ transients in CA1 pyramidal neurons. TNC−/− mice showed normal learning and memory in the contextual fear conditioning paradigm but impaired extinction of conditioned fear responses. Systemic injection of the L-VGCC blockers nifedipine and diltiazem into wild-type mice mimicked the impairment of fear extinction observed in TNC−/− mice. The deficiency in TNC−/− mice substantially occluded the effects of these drugs. Our results suggest that TNC-mediated modulation of L-VGCC activity is essential for fear extinction

Non-HDL cholesterol predicts coronary heart disease in primary prevention: findings from an Italian a 40-69 year-old cohort in general practice

Scopo. La frazione lipoproteica denominata “colesterolo non-HDL” viene raccomandata come un indice di rischio coronarico (RC) associata alla dislipidemia combinata ed è stata trovata un utile fattore predittivo del rischio coronarico nei pazienti diabetici. Abbiamo studiato l’associazione tra i fattori di RC noti, incluso la colesterolo non-HDL ed una “condizione di RC elevato”, cioè un “RC a 5-anni >15%” in medicina generale. Metodi. Abbiamo studiato 4085 individui di età 40-69 anni, 489 diabetici e 3596 non-diabetici, appartenenti ad una coorte opportunistica. Sono state utilizzate le statistiche descrittive, e la regressione logistica multivariata aggiustata per età e sesso per i confronti tra i 2 gruppi. Risultati. Circa il 12% dei participanti era diabetico. I confronti aggiustati per età e sesso hanno mostrato che tutte le variabili erano significativamente peggiori nei diabetici rispetto ai non-diabetici (eccetto fumo, colesterolo totale e rapporto colesterolo totale/HDL). I diabetici avevano un “RC medio a 5-anni” più alto dei non-diabetici (18.8±11.9% vs 7.5±6.9%, P15%” (55.4% vs 11.1%, P<0.01). Nei diabetici, le variabili associate ad una “condizione di RC elevato” sono: fumo, pressione arteriosa sistolica (PAS) e colesterolemia non-HDL; nei non-diabetici: fumo, PAS, colesterolemia non-HDL e HDL (inversamente). Conclusioni. Il colesterolo non-HDL – oltre a fumo e PAS – è un forte predittore di una “condizione di RC elevato” sia negli individui diabetici che non-diabetici