Peripheral neuropathy is a common adverse effect of bortezomib-based chemotherapy. In this study we have investigated the role played by subtype 5 of metabotropic receptors in bortezomib induced ...peripheral neuropathy. Rats were administered with bortezomib three times weekly at 0.20 mg/kg for a total of 4 weeks in presence or absence of mGluR5 antagonist MPEP. The animals were submitted to paw-pressure test and tail sensory nerve conduction measurement more times during the treatment and follow-up. Bortezomib treatment induced a progressively increasing hyperalgesia in rat which was accompanied by a significant reduction in sensory nerve conduction velocity (SNCV). MPEP prevented the emergence of bortezomib-induced pain and counteracted SNCV reduction when co-administered with bortezomib treatment. Spinal extracellular glutamate levels increased in rats treated with bortezomib. Bortezomib-induced onset of the hyperalgesia and SNCV decrease could be prevented by agents that promote the reuptake of glutamate maintaining spinal glutamate at basal level. Our data support the manipulation of the glutamatergic system through the mGluR5 receptor in bortezomib induced peripheral neuropathy. The use of antagonists at the mGluR5, initiated at the same time as bortezomib-chemotherapy, might reduce the number of patients who develop painful peripheral chemo-neuropathy.
•Glutamate dysregulation is a key element in neuropathic pathogenesis elucidation.•mGluR5 was involved in neuropathic pain caused by nerve injury and diabetes.•Bortezomib induced neuropathic pain was prevented in rodent by antagonism to mGluR5.•Onset of hyperalgesia was turned off by agents promoting glutamate uptake.•Manipulation of glutamatergic system underlies bortezomib induced peripheral neuropathy.
Abstract Behçet's 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.
To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities.
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°.
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).
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.
Purpose
To report the clinical course and management of unusual anterior and posterior segment features of Coats disease and their relation to the age of the patients to increase the awareness ...towards these rare clinical features rarely described in the current literature.
Methods
A retrospective descriptive review of 45 eyes of 45 patients affected by Coats disease was conducted at the Retinoblastoma Referral Center and Ophthalmology Unit of the University of Siena in Italy analyzing data from 2000 to 2022. Medical records and images were revised to find some cases presenting unusual anterior and posterior segment features in patients affected by Coats disease.
We identified therefore 4 unusual clinical conditions: retinal macrocysts, anterior chamber cholesterolosis, fovea-sparing Coats disease and secondary vasoproliferative tumor.
Results
Two patients presented with retinal macrocyst (2/45 = 4.4%), one with anterior chamber cholesterolosis (1/45 = 2.2%), two with fovea sparing Coats disease (2/45 = 4.4%) and one with vasoproliferative tumor associated (1/45 = 2.2%) for a total of six (6/45 = 13.3%) patients manifesting unusual anterior or posterior segment features in Coats disease.
Conclusion
Unusual anterior and posterior segment features of Coats disease such as retinal macrocyst and anterior chamber cholesterolosis have been more frequently reported in younger children while fovea-sparing and vasoproliferative tumors have been more commonly described in older patients. Age is then a strong prognostic marker which allows to distinguish two different phenotypes of Coats disease: patients younger and older than 3 years old with more aggressive and milder phenotype respectively.
We report three cases of congenital medulloepithelioma, which is an extremely rare clinical pattern of a tumor rare by definition. The aim of this study is to underline the clinical features of ...advanced medulloepithelioma in newborns.
Background and Purpose
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.
Experimental Approach
In the social learning test, an adult rat investigates a juvenile. The juvenile is submitted to a second encounter after a few days and investigation by the adult should be reduced. Morphine was administered before the first encounter between rats, and the critical test was performed 24, 72 or 168 h later, when animals were re‐exposed to each other, in the absence of morphine.
Key Results
Low doses of morphine, comparable with endogenous brain concentrations, enhanced long‐term memory recognition; while high doses did the reverse, indicating the adult failed to recognize the juvenile. Recognition of a familiar rat appeared to be mediated within the brain accessory olfactory bulb (AOB) by an opioid system intrinsic to the olfactory system through μ‐opioid receptors (MORs). At this supraspinal site, the PLC/PKC signalling pathway was activated by extremely low morphine doses.
Conclusions and Implications
Morphine treatment administration may either disrupt or facilitate social memory, depending on the dose, extending to memory formation the bimodal effects of morphine previously shown in pain. Social memory formation elicited by extremely low morphine doses, was mediated within the AOB by an opioid system, intrinsic to the olfactory system through MORs.
Purpose:
To evaluate the rarity, clinical features and management of Coats disease characterized by fovea-sparing enhancing the importance of pediatric retinal screening and early management to ...maintain a good visual acuity.
Methods:
Retrospective analysis of approximately 40 patients affected by Coats disease between 2000 and 2020 at the Retinoblastoma Referral Center and Ophthalmology unit of the University of Siena in Italy.
Results:
Two patients with fovea sparing Coats disease were included. Both presented an extrafoveal Coats disease (stage 2A by Shields classification) when they were 5 and 6 years old respectively.
They had no anterior findings and a presenting visual acuity of 20/20 reflecting the early stage and a milder phenotype of the disease which are indeed more likely to be found in patients older than 3 years at presentation.
Both presented telangiectasia and retinal exudation in the affected eye. Standard Argon laser photocoagulation and subsequently Cryotherapy were performed in the telangiectatic retinal periphery of both patients obtaining an excellent control and regression of the disease.
Conclusions:
Careful pediatric retinal screening and early management are crucial to ensure a good visual prognosis in such an early feature of Coats disease as fovea sparing since this condition unfortunately tends to recall the physician’s attention in more advanced stages.
Due to the extremely poor number of articles regarding such a rare feature of Coats disease like fovea sparing, we report our experience.
Vasoproliferative retinal tumors in children and adults Hadjistilianou, Doris; De Francesco, Sonia; Menicacci, Cristina ...
Acta ophthalmologica (Oxford, England),
December 2019, 2019-12-00, 20191201, Letnik:
97, Številka:
S263
Journal Article
Recenzirano
Purpose
Vasoproliferative tumors of the retina (VPTR) are benign lesions of unknown origin that may occur isolated (primary) or in association with other ocular conditions (secondary). They may be ...unilateral or bilateral and have a predilection for the peripheral inferior temporal quadrant of the retina. Retinal vasoproliferative tumors may be present at any age, although the majority are present in the third and fourth decades of life.
Methods
The authors report a personal series of cases in young children and adults either idiopathic or secondary to a pre‐existing ocular disease (retinitis pigmentosa and Nf1).
Results
Clinical findings, imaging, therapeutic options and outcome are reported.
Conclusions
Retinal vasoproliferative tumors may be idiopathic (74%) or secondary to a pre‐existing ocular diseases (26%). The fundus quadrant location in these tumors is curiously weighted toward the inferotemporal region. Despite this, these tumors may effect the visual activity because of the associated retinovitreal findings, such as subretinal and/or intraretinal exudation, subretinal fluid, vitreous hemorrhage, preretinal macular fibrosis and macular edema.
: 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.
: 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.
: 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.
: 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.
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