Paola Di Mauro

Heat shock proteins and hormesis in the diagnosis and treatment of neurodegenerative diseases

Modulation of endogenous cellular defense mechanisms via the vitagene system represents an innovative approach to therapeutic intervention in diseases causing chronic tissue damage, such as in neurodegeneration. The possibility of high-throughoutput screening using proteomic techniques, particularly redox proteomics, provide more comprehensive overview of the interaction of proteins, as well as the interplay among processes involved in neuroprotection. Here by introducing the hormetic dose response concept, the mechanistic foundations and applications to the field of neuroprotection, we discuss the emerging role of heat shock protein as prominent member of vitagene network in neuroprotection and redox proteomics as a tool for investigating redox modulation of stress responsive vitagenes. Hormetic mechanisms are reviewed as possibility of targeted therapeutic manipulation in a cell-, tissue- and/or pathway-specific manner at appropriate points in the neurodegenerative disease process.

Epilepsy and innate immune system: A possible immunogenic predisposition and related therapeutic implications

Recent experimental studies and pathological analyses of patient brain tissue samples with refractory epilepsy suggest that inflammatory processes and neuroinflammation plays a key-role in the etiopathology of epilepsy and convulsive disorders. These inflammatory processes lead to the secretion of pro-inflammatory cytokines responsible for blood-brain-barrier disruption and involvement of resident immune cells in the inflammation pathway, occurring within the Central Nervous System (CNS). These elements are produced through activation of Toll-Like Receptors (TLRs) by exogenous and endogenous ligands thereby increasing expression of cytokines and co-stimulatory molecules through the activation of TLRs 2, 3, 4, and 9 as reported in murine studies.It has been demonstrated that IL-1β intracellular signaling and cascade is able to alter the neuronal excitability without cell loss. The activation of the IL-1β/ IL-1β R axis is strictly linked to the secretion of the intracellular protein MyD88, which interacts with other cell surface receptors, such as TLR4 during pathogenic recognition. Furthermore, TLR-signaling pathways are able to recognize molecules released from damaged tissues, such as damage-associated molecular patterns/proteins (DAMPs). Among these molecules, High-mobility group box-1 (HMGB1) is a component of chromatin that is passively released from necrotic cells and actively released by cells that are subject to profound stress. Moreover, recent studies have described models of epilepsy induced by the administration of bicuculline and kainic acid that highlight the nature of HMGB1-TLR4 interactions, their intracellular signaling pathway as well as their role in ictiogenesis and epileptic recurrence.The aim of our review is to focus on different branches of innate immunity and their role in epilepsy, emphasizing the role of immune related molecules in epileptogenesis and highlighting the research implications for novel therapeutic strategies.

The usefulness of immunotherapy in pediatric neurodegenerative disorders: A systematic review of literature data

Immunotherapeutic strategies to treat neurodegenerative disorders have inspired the scientific community. The aim of our review is to address the translational aspects of neuroimmunology to describe the efficacy of immunotherapy in the treatment of pediatric neurodegenerative disorders. In the studies we analyzed IVIG were found to be efficient in the treatment of post-streptococcal neurodegenerative disorders, even if in PANDAS, plasma-exchange (PE) showed a higher efficiency. IVIG were also successfully used in ADEM and Guillan-Barré syndrome. In Sydenham Chorea the use of methylprednisolone was found in most cases as efficient as IVIG, while in Tourettes Syndrome, Colecoxib was successfully used in one patient. Pediatric Multiple Sclerosis seems to respond better to immunosuppressant agents (Mitoxantrone, Cyclophosphamide, Natalizumab), as well as Neuromyelitis optica (Rituximab, Mycofenolate). The importance of this review relies in the attempt to draw standardized guidelines for immunotherapy in pediatric neurodegeneratve disorders

The senile functional evolution of the larynx after supracricoid reconstructive surgery

Supracricoid partial laryngectomy is a relevant organ-preserving surgical technique used for the treatment of early or locally advanced laryngeal tumors with an oncologic outcome comparable with that of total laryngectomy. This reconstructive surgery is certainly technically feasible also in the elderly, but the problem is postoperatively as the patient may lack the will and strength to be successfully rehabilitated. The goal was to evaluate functional outcomes, in a maximum follow-up period of ten years from the end of the postoperative follow-up, in a cohort of elderly patients to look at the senile evolution of the laryngeal post surgical function comparing the amount of resection and grade of possible impairment of swallowing and phonatory parameters. A group of 33 patients were selected for a retrospective study aimed at evaluating the long-term evolution of laryngeal functionality after surgery, with the baseline at 5 years from the end of follow-up. All the patients had three-monthly visits for a period up to ten years, during which the objective and subjective swallowing and phonatory parameters were recorded, analyzed and, at the end of the study, compared with baseline. The results suggest that long-term post surgical functional problems may develop also in the neolarynx where the effects of the reconstructive surgery, on speech and swallowing, are largely stabilized. The presence of arytenoid resection had significantly impacted on the occurrence of aspiration even if the overall number of dysphagic patients was not statistically significant compared to baseline.

Multicenter research into the quality of life of patients with advanced oropharyngeal carcinoma with long‑term survival associated with human papilloma virus

The treatment of advanced-stage oropharyngeal squamous cell carcinoma may utilize various modes, including combining surgery with chemoradiotherapy (CTRT), or primary CTRT followed by rescue surgery. In previous literature it has been revealed how patients treated with combined modes report a low quality of life (QoL) and severe consequences following surgery, radiotherapy and chemotherapy, in the short and in the long-term. The decrease in the QoL of patients treated with high-intensity multi-modal strategies highlights the necessity of modifying treatments, particularly for young HPV-positive patients, where an increased survival rate has already been reported. The modified treatment for HPV-positive tumors in the tonsils and at the base of the tongue is based on the deintensification of therapies aiming to reduce toxicity and thereby improve QoL in the long term, whilst still maintaining therapeutic effectiveness. The aim of the present study was to evaluate the QoL in patients with a long-term survival, who were treated with combined therapy for squamous cell tumors in the tonsils and at the base of the tongue, and to compare the results observed in HPV-positive and HPV-negative patients. According to statistical analysis, differences in the general QoL and in the single scales of the European Organization for the Research and Treatment of Cancer questionnaires were not correlated with the type of therapy selected for the particular patient. QoL considered the presence of HPV, the type of treatment, the subregion of the tonsils vs. the base of the tongue and the disease stage at the time of diagnosis, and was determined to be non-influential with regard to these specific variables.

Neurovegetative disorders of perimenopausal women treated with docosahexaenoic acid (DHA, 625 mg)

Abstract The study evaluated the effect of DHA 625 mg in women who experience menopausal symptoms, on sexuality and quality of life (QoL), and on the auditory brainstem response (ABR). Forty-two perimenopausal women were enrolled. The Kupperman Index (KI) was used to evaluate menopause symptoms. The Short Form-36 (SF-36), Female Sexual Function Index (FSFI), and the Female Sexual Distress Scale (FSDS) were used to assess QoL, sexual function, and sexual distress, respectively. Auditory evoked potentials to measure the ABR. The study had one follow-up at 6 months. The women reported an improvement in the KI total score (p < .001). Moreover, women reported QoL improvements in all the psychological categories (p < .001), but not in physical categories (p = NS). FSFI and FSDS total scores increased (p < .01) and the FSDS score decreased (p < .01), mainly due to arousal (p < .03) and lubrication (p < .05) sexual aspects. The ABR wave latencies were lower than the baseline values (p < .05). DHA could be effective in modulating some perimenopausal symptoms in women and, consequently could contribute to improve their QoL and sexual life. Finally, DHA seems to have a direct activity on the neuronal conduction time into the audiological system.

Expression pattern of estroprogestinic receptors in sinonasal inverted papilloma

Inverted papilloma (IP) is a locally destructive, benign neoplasm of the nose and paranasal sinuses with a high tendency for recurrence, a significant potential for malignancy, and an etiology that today is still uncertain. The expression of hormonal receptors in neoplastic tissues has been the focus of intensive research for its potential diagnostic, prognostic, and therapeutic significance. The aim of this study was to assess the potential estroprogestinic receptor expression in patients undergoing sinus surgery for IP. A retrospective study was carried out, on surgical specimens of 73 patients who underwent endoscopic sinus surgery for first manifestation of sinonasal IP (primitive IP group) and in 21 subjects who had developed a recurrence (relapsed IP group). The results of the immunohistochemical analysis of the first group showed the absence of receptor expression for PGR in all cases analyzed and the presence of a low positivity for ER in 11 cases (P > 0.082). Similarly, in the second group the results showed a low presence of ER receptors in 3 of the 21 cases (P > 0.068), while there was no evidence of PGR receptors in the examined samples. In addition, in 11 of the cases only 3 were considered positive (27.2%) showing a recurrence during follow-up (P > 0.068). Our results suggest that the sinonasal IP is a benign tumor independent of estrogen and progesterone, and the receptors for these hormones are therefore unsuitable as predictors of relapse or possible prognostic indicators and therapeutic targets.

Therapeutic approaches to pediatric pseudotumor cerebri: New insights from literature data.

The pseudotumor cerebri syndrome (PTCS), also known as idiopathic intracranial hypertension (IIH), is characterized by signs and symptoms of increased intracranial pressure such as headache and cranial nerve palsies, in the absence of any space-occupying mass. This condition commonly affects overweight women of childbearing age, even if it is also frequent in men and children. Children with PTCS may present with atypical signs and symptoms, with a different prognosis compared to adults. However, the treatment is the same for both children and adults, even if there are no strict treatment guidelines in regards. All treatment strategies in children are based on retrospective studies and none has been evaluated in prospective or randomized controlled trial studies. This review focuses on literature data on PTCS treatment in children.

Use of Videodermatoscopy in Scalp Disorders

Videodermatoscopy is a new technique that, allowing the visualization at high magnification (×10 to ×1,000) of hair and scalp skin, has been increasingly and successfully used in the evaluation of different hair and scalp disorders. In particular, VD may be useful for the diagnosis and follow-up of different types of hair loss (androgenetic alopecia, alopecia areata, telogen effluvium, trichotillomania, congenital triangular alopecia, tinea capitis, scarring alopecia), parasitic and inflammatory scalp diseases, and hair shaft disorders.