Cristina Menicacci

Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behçet's disease

Behçets disease (BD) is a multi-systemic disorder of unknown etiology characterized by relapsing oral-genital ulcers, uveitis, and involvement of the articular, gastrointestinal, neurologic, and vascular systems. Although the primum movens of this condition remains unknown, a tangled plot combining autoimmune and autoinflammatory pathways has been hypothesized to explain its start and recurrence. In-depth analysis of BD pathogenetic mechanisms, involving dysfunction of multiple proinflammatory molecules, has opened new modalities of treatment: different agents targeting interleukin-1 have been studied in recent years to manage the most difficult and multi-resistant cases of BD. Growing experience with anakinra, canakinumab and gevokizumab is discussed in this review, highlighting the relative efficacy of each drug upon the protean BD clinical manifestations. Safety and tolerability of interleukin-1 antagonists in different doses have been confirmed by numerous observational studies on both large and small cohorts of patients with BD. In particular, the potential for Mycobacterium tuberculosis reactivation and tuberculosis development appears to be significantly lower with interleukin-1 blockers compared to tumor necrosis factor-α inhibitors, thus increasing the beneficial profile of this approach.

In vivo confocal microscopy of conjunctiva in preservative‐free timolol 0.1% gel formulation therapy for glaucoma

To evaluate the effects at 1 year of preservative‐free timolol gel and preserved timolol eye drops on conjunctiva and tear parameters.

Blindness and Glaucoma: A Multicenter Data Review from 7 Academic Eye Clinics

Purpose To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. Methods This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder (‘controls’). Blindness was defined as visual acuity≤0.05 and/or visual field loss to less than 10°. Results Unilateral and bilateral blindness were respectively 11.0% and 1.6% at the beginning, and 15.5% and 3.6% at the end of the observation period (7.5±5.5 years, range:1–25 years); conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14% in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). Conclusions In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved; it could be predicted by high initial MD, high initial IOP, and old age.

Prophylactic role of acetyl-l-carnitine on knee lesions and associated pain in a rat model of osteoarthritis

AIMS in the present study, our aim was to validate in vivo the prophylactic role of acetyl-l-carnitine (ALC) using an established knee osteoarthritis (OA) animal model which mimics the pathological changes of OA in humans, targeting cartilage and causing chondrocyte death. MAIN METHODS animal model was obtained by an intra-articular injection of monosodium iodoacetate (MIA) into rat femorotibial joint space. Pain was measured in animals submitted to MIA model by paw pressure and compression behavioral tests in the presence or absence of ALC. KEY FINDINGS morphological analysis of knee-joint from MIA and ALC co-treated rats showed that the total pathological score attributed to histological findings was dramatically lower in rats treated with MIA in the presence of ALC. OA chondrocyte overexpression of pathogenic collagenase matrix-metallopeptidase-13 (MMP13) could be decreased in knee-cartilage from MIA/ALC rats; whereas type II collagen (COL2) expression level could be partially increased to control value. ALC twice daily treatment was able to attenuate pain in OA rat knee as revealed by mechanical behavioral tests. SIGNIFICANCE in our experiments, pain that is usually associated with OA, was correlated with the severity of histopathological findings. Our findings show that there is a place for ALC as chondroprotective agents in cartilage degradation and strongly support the prophylactic and therapeutic potentials of ALC in knee-OA patients.

Dual effect of morphine in long-term social memory in rat

Bimodal dose–response relationships have been demonstrated in animals and humans following morphine administration. We examined if systemic administration of morphine, in extremely low (μg) and high (mg, analgesic) doses, changed the learning process.

Contribution of G inhibitory protein alpha subunits in paradoxical hyperalgesia elicited by exceedingly low doses of morphine in mice

AIMS Although morphine, at higher doses, induces analgesia, it may also enhance sensitivity to pain at extremely low doses as shown in studies for testing an animals sensitivity to pain. We used an antisense approach capable of selectively down-regulating in vivo G(i)(G inhibitory protein),G(o) and G(s) members of the G(α) sub-family protein subunits in order to establish if these proteins might be implicated in the effects induced by extremely low morphine doses on acute thermonociception. MAIN METHODS Mice pretreated with a morphine hyperalgesic dose (1μg/kg) were submitted to hot plate test after pre-treatment with antisense oligodeoxynucleotides (aODNs) targeting G(iα), G(oα) and G(sα) regulatory proteins. The association of G-protein (guanine nucleotide-binding regulatory protein) coupled receptors with G protein was investigated using co-immunoprecipitation procedure. KEY FINDINGS The downregulation of the G(iα1-3) and G(oα1) proteins reversed the licking latency responses induced by 1μg/kg morphine administration toward the basal value whereas downregulation of the G(oα2) and G(sα) proteins did not significantly modify the hyperalgesic response. SIGNIFICANCE These results suggest that G inhibitory proteins play a role in the production of low dose evoked morphine hyperalgesia in mouse. Immunoprecipitation studies revealed that both μ opioid receptor (μOR) and α(2) adrenoreceptor (α(2) AR) are bound to G inhibitory proteins in hyperalgesic response to morphine extremely low dose. Both μOR and α(2) AR appear to be necessary for low morphine dose induced hyperalgesic response through G inhibitory proteins.

13q deletion syndrome and retinoblastoma in identical dichorionic diamniotic monozygotic twins.

Purpose To report the case of identical dichorionic diamniotic female twins with unilateral retinoblastoma in 13q deletion syndrome. Methods Clinical and ophthalmoscopic evaluation, combination of multiple ligation-dependent probe amplification, array–comparative genomic hybridization analyses, and magnetic resonance imaging were performed. Results Peculiar facial features, marked hypotonia, gastroesophageal reflux, interatrial septal defect with left to right shunt and light dilatation of right chambers, 5th finger hypoplasia, 3rd-5th toes clinodactyly, 2nd toe overlapped to 3rd toe, and cutis marmorata were found. Ophthalmoscopic evaluation revealed unilateral retinoblastoma in both girls. Magnetic resonance imaging detected corpus callosum hypoplasia in both twins. A 34.4-Mb deletion involving bands 13q13.2-q21.33 and including the RB1 gene was identified in both twins. The deletion was not present in the DNA of their parents and older brother. Conclusions Dysmorphic features in children must be always suspicious of 13q deletion syndrome and a short ophthalmoscopic follow-up is necessary to detect the presence of a retinoblastoma.

Use of hypo-osmolar riboflavin for corneal cross-linking in thin keratoconic corneas

Purpose To evaluate the efficacy of UVA collagen cross linking (CXL) on thin keratoconic corneas with previous application of hypoosmolar riboflavin solution.

I-LASIK retreatment of residual refractive errors after microkeratome and femtosecond assisted LASIK

Purpose To evaluate the efficacy and safety of femtosecond‐assisted sub‐bowman keratomileusis (I‐LASIK) retreatment for residual refractive errors after either I‐LASIK or microkeratome assisted LASIK.