RESUMO
OBJECTIVE: High-pressure physiological saline isotonic solution (HPpSIS) delivery into the nasal cavity was found to modulate the local expression of immune cells, increase NGF protein, and enhance the NGF receptors' expression. Since the nasal cavity directly communicates with the eye and as NGF was previously found to ameliorate the symptoms of dry eye when topically delivered, the aim of this study was to establish whether the HPpSIS might ameliorate ocular dryness and tear film composition. SUBJECTS AND METHODS: This is an observational self-controlled case study carried out on 16 patients with dry-eye diagnosis, concerning 3-month self-administration of HPpSIS and two serial assessments of the ocular surface and tear film. OSDI questionnaire was used for ocular symptoms of dryness. BUT and Schirmer tests were used for qualitative and quantitative tear film analysis. The lipid composition was also examined. R-studio was employed for the detection of the difference between the pre- and post-analysis. RESULTS: On the basis of the OSDI questionnaire, the study population was divided into severe (61.1%), moderate (5.5%), and mild (16.6%) dry-eye symptoms. OSDI score was significantly reduced after HPpSIS (p<0.05). BUT and TMH values also ameliorated after HPpSIS (p>0.05), although not significantly. The lipid layer improved statistically (p<0.05) and correlated positively with OSDI grading. The variability of presentation in the numerical distribution before and after therapy suggests poor test sensitivity. CONCLUSIONS: HPpSIS showed a positive effect in reducing OSDI scores and ameliorating tear film quality. The possibility of an endogenous HPpSIS-induced NGF should be taken into account in dry-eye therapy.
Assuntos
Síndromes do Olho Seco , Humanos , Projetos Piloto , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/diagnóstico , Lágrimas , Solução Salina , Soluções Isotônicas/metabolismo , LipídeosRESUMO
OBJECTIVE: In a previous study, we reported an increase of nasal nerve growth factor (NGF) in patients treated with high-pressure administration of sterile saline isotonic solution (HPpSIS). Herein we characterized the nasal mucosa in terms of innate immune response and cytokine signature, including antiviral properties. Potential NGF and antiviral benefits of HPpSIS were also discussed. PATIENTS AND METHODS: Twenty (20) patients (11 males, 9 females; age range 30-75 years old) underwent HPpSIS and nasal samples were collected before and after treatment. Nasal scraping was used for morphological (smears and Quick May-Grunwald Giemsa staining, MGG), biochemical (Histamine, Serotonin; ELISA) and molecular (messenger RNA, mRNA) analyses. Amplification of transcripts specific for Toll-like receptor (TLR) 3 (TLR3), TLR7, TLR9, Interleukin-(IL) 18 (IL18), IL13, IL12, eosinophil-derived neurotoxin (EDN), Eosinophil Cationic Protein (ECP), γ Interferon (γIFN), tryptase and serotonin was performed using the 2-step real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR). Clinical and laboratory data were analyzed and compared. RESULTS: The clinical evaluation showed a protective effect of our therapy. Smears showed the presence of leucocytes, eosinophils (EOs) and mast cells (MCs), and increased immunoreactivity for ECP/RNase3 and EDN after HPpSIS. ELISA showed increased levels of Serotonin and EDN associated with unchanged levels of substance P(SP) and histamine. Increased eosinophil-derived neurotoxin eosinophil-derived neurotoxin (EDN) levels were confirmed by in situ fluorescent analysis. HPpSIS induced the upregulation of TLR3, TLR7 and TLR9 transcripts, while no changes were observed for Intercellular Adhesion Molecule 1 (ICAM1), IL18, Interleukin-15 (IL15) and IL12 transcripts nor for Interleukin-6 (IL6) and IL13. No changes were also observed for γIFN and EDN/RNase2 transcripts, while ECP/RNase3 transcripts were significantly upregulated after HPpSIS. Finally, tryptase transcripts were unchanged while serotonin transcripts were significantly increased after HPpSIS. CONCLUSIONS: The clinical and biomolecular changes observed at the nasal mucosa due to HpSS treatment suggest the activation of an innate surveillance, by means of TLR transcription, and a possible anti-viral response due to EDN upregulation. It remains to be verified if NGF, known to be released locally upon HpSIS treatment, might in part be responsible for this local activation.
Assuntos
Interleucina-18 , Receptor 3 Toll-Like , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Neurotoxina Derivada de Eosinófilo/genética , Neurotoxina Derivada de Eosinófilo/metabolismo , Interleucina-18/metabolismo , Receptor 3 Toll-Like/metabolismo , Triptases , Fator de Crescimento Neural/metabolismo , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Histamina/metabolismo , Interleucina-13 , Serotonina/metabolismo , Proteína Catiônica de Eosinófilo/metabolismo , Eosinófilos , Antivirais/farmacologia , Antivirais/metabolismo , Interleucina-12/metabolismoRESUMO
OBJECTIVE: Serotonin, which is a vasoactive amine, is an important neurotransmitter and is involved in many behavioral and psychological phenomena, such as pain, appetite, mood, and sleep. The primary purpose of our study was to investigate the effect of high-pressure administration of sterile physiological saline isotonic solution (HpPSIS) into nasal cavity and to determine the expression of the serotonin. PATIENTS AND METHODS: The study was made in two branches, the previous with 14 volunteers, the subsequent study with 40 patients with mild anxiety disorder. The middle third of the inferior turbinate epithelial cells on the right nostril was scraped using a sterile curette and indicated as (pre), then, a spray of sterilized isotonic solution at high pressure on the left nostril was delivered, and 5 minutes later a similar stimulation was delivered on the same nostril. The stimulation was made with a specific spray dispenser. The middle third of the inferior turbinate epithelial cells on the left nostril was scraped using a sterile curette and indicated as (post). Then, based on the first part of our study, we started the second part and gave a treatment on forty new patients with anxiety disorder. RESULTS: The results of these studies highlight the possibility of endogenous enhancement of serotonin by stimulation of mast cells. In the first part of the study, Serotonin significantly increased in protein extracts after treatment (64.35±5.33 vs. 10.97±2.17; unpaired two tailed t-test, t=9.8, df=24, p≤0.0001; F=6.035; DFn=12; DFd=12). In the second part of the study, in patients treated with HpPSIS, we observed improvement of mood, after one, two and three months, with a statistically significant reduction of DASS-21, while no reduction was observed in control patients, treated with normal pressure commercial spray. CONCLUSIONS: This pilot study showed that the topical treatment of HpPHIS increases serotonin levels in nasal cavity. The observation reported in this study opens the way to a new valid strategy to enhance the level of endogenous serotonin. We observed a significant improvement of ASI on patients during HpPHIS therapy.
Assuntos
Cavidade Nasal , Serotonina , Administração Intranasal , Humanos , Soluções Isotônicas/metabolismo , Soluções Isotônicas/farmacologia , Cavidade Nasal/metabolismo , Projetos Piloto , Serotonina/metabolismoRESUMO
OBJECTIVE: This study aims to evaluate the effect of trans-resveratrol/carboxymethylated (1.3/1.6)-ß-d-glucan administered via nasal, after FESS, assessing nasal respiratory distress and nasal mucosa healing. PATIENTS AND METHODS: We enrolled 70 patients, from March 2019 to February 2020, with chronic nasal obstruction not responding to medical therapy and candidates to endoscopic nasal surgery. Patients were divided in two non-randomized groups: group A treated with trans-resveratrol/carboxymethylated (1.3/1.6)-ß-d-glucan administered via nasal, and group B treated with 0.9% nasal irrigation saline. Patients were clinically evaluated, in post-operative period, at 7 (T0), 15 (T1), and 30 days (T2) with fibroendoscopy. The CRS (chronic rhinosinusitis) questionnaire (Snot 20) was administrated at T0, T1, and T2. The findings were scored with respect to middle turbinate edema. In both Groups, the inferior turbinate's medial aspect was scraped using a sterile disposable Rhino-probe mucosal curette (Arlington Scientific, Inc., Springville, UT, USA) at T0, T1, and T2. RESULTS: Group A showed an improvement in Snot 20 in T1 and T2 both. The reduction of the mucosal edema and nasal secretion has been statistically significant in the Group A. A slight cell reduction was observed at T2 with respect to T1. This decreased pattern is more evident in nasal scraping from Group A. The appearance of epithelial cells at T2 of Group A is consistent with the reduction of inflammatory cells. CONCLUSIONS: We can assert that in Group A it appears less evident the presence of edema, nasal congestion and crusts, resulting in a quick recover.
Assuntos
Glucanos/uso terapêutico , Mucosa Nasal/efeitos dos fármacos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Resveratrol/uso terapêutico , Sinusite/tratamento farmacológico , Administração Intranasal , Adulto , Endoscopia , Feminino , Glucanos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/cirurgia , Cuidados Pós-Operatórios , Síndrome do Desconforto Respiratório/cirurgia , Resveratrol/administração & dosagem , Sinusite/cirurgia , Adulto JovemRESUMO
OBJECTIVE: In the present study, we investigated whether high-pressure hypotonic saline solution (Hphss) affects the basal level of Nerve Growth Factor (NGF) and expression of receptors in the cochlea, bark earing, retina, and visual cortex. MATERIALS AND METHODS: For this study, we used three weeks old female Sprague Dawley (SD) rats (n = 12). Rats were housed in polypropylene cages and were kept under standard conditions (12 h light:12 h dark cycle) with free access to water and food (Purina chow food). A specific dispenser was employed to deliver sterile hypotonic saline at high pressure (pressing emission level (PEL): 7 g/s; emission time (ET): 0.5 s). Rats were divided into two groups: untreated (n = 6) and treated with Hphss (n = 6), three times per day, for 10 consecutive days. Treatment was performed in both nostrils with 50 µl of Hphss using a microsyringe equipped with a plastic tip. RESULTS: We observed a significant enhancement in the level of NGF in the cochlea and bark earing, but not in the retina and visual cortex. This is likely because the nasolacrimal duct pathway does not appear to have an effect on the retina, and the visual cortex appears to be too far from the cribriform plate to be reached by nasal NGF. CONCLUSIONS: This treatment can significantly protect and/or delay degeneration of cochlear auditory NGF-target cells. It is free from side effects and can be used in chronic diseases for as long as needed. It remains to be investigated whether the effects of short-term therapy are long-lasting, or if the treatment must be repeated.
Assuntos
Vias Auditivas/metabolismo , Cóclea/metabolismo , Fator de Crescimento Neural/metabolismo , Retina/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Nerve Growth Factor (NGF) is a neurotrophic factor known to play a critical role in growth, survival, differentiation and neuroprotection of peripheral sensory and sympathetic neurons, as well as brain neurons. We have recently reported that nasal administration of high-pressure isotonic physiological saline solution (HPpSIS) enhances the level of NGF and the expression of NGF receptors in neurons of the olfactory bulbs and forebrain cholinergic neurons of laboratory animals. In the present study, we sought to determine whether the same treatment affects the levels of NGF within the brain tumor tissue. PATIENTS AND METHODS: This study was conducted on eight adult patients, 4 males and 4 females with malignant anterior cranial fossa tumor. Before surgery, four subjects, two males and two females received nasal administration of HPpSIS for ten consecutive days. RESULTS: The levels of NGF in surgical removed peripheral tumor brain samples of patients treated with nasal HPpSIS administration are more elevated compared to the levels of NGF in peripheral brain tissues of HPpSIS untreated patients. CONCLUSIONS: We observed that nasal administration of HPpSIS enhances not only the basal brain NGF levels and the expression of NGF receptors but also the tumor suppressor protein p73. The possible functional significance of these observations will be described and discussed.
Assuntos
Neoplasias Encefálicas/metabolismo , Fator de Crescimento Neural/metabolismo , Neurônios/metabolismo , Cloreto de Sódio/administração & dosagem , Proteína Tumoral p73/metabolismo , Administração Intranasal , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Fator de Crescimento Neural/metabolismo , Soluções/administração & dosagemRESUMO
OBJECTIVE: Nerve growth factor (NGF) is a neurotrophin which promotes and regulates the survival of neurons in the peripheral nervous system. The aim of this study was to investigate the effect of high-pressure administration of sterile physiological saline isotonic solution (HpPSIS) into nasal cavity of laboratory animals on NGF levels and NGF-receptor expression in the olfactory bulbs and brain. MATERIALS AND METHODS: For this study we used three weeks old female Sprague Dawley SD rats (n=48). Rats were divided into two groups, the first one treated delivering physiological saline solution with a normal syringe modified at the extremity to fit the rats' nostril (5 ml) (n=24) and the second one treated spray with HpPSIS (n=24 rats). Rats were treated three times a day either for 5 consecutive days (shorth term treatment) or 10 consecutive days (longer treatment) in both nostrils of HpPSIS delivered at high pressure (pression emission level: PEL: 7 g/sec for emission time ET: 0.5 sec) with a specific forced spray erogator. Untreated rats received a similar manipulation three times a day through a syringe in the nostrils, but no HpPSIS administration. RESULTS: The results of these studies highlight the possibility that endogenous enhancement of NGF by stimulation of NGF-producing cells within the nasal cavities and also in the CNS represent a novel experimental approach to enhance the brain NGF levels with a new therapy. HpPSIS treatment further enhances the presence of NGF in the four brains examined. Indeed, a significant increase of NGF was first observed after 5 days of HpPSIS treatment, compared to HpPSIS untreated rats. The increase was over 25% in the OB, ST, HI and in CX, while 10 days after HpPSIS treatments the levels of NGF were even higher. These differences were statistically significant, p < 0.05. CONCLUSIONS: It was found that forced administration of HpPSIS enhances the presence of these neurotrophic signals, not only in the olfactory bulbs, but also in forebrain cholinergic neurons, which are known to degenerate as result of memory loss and brain aging, including Alzheimer Disease. These findings for the first time in the literature demonstrate the possibility of enhancing the endogenous NGF to protect NGF-damaged neurons. Since the enhanced expression of NGF was first observed after 5 days of treatment and higher after 10 days of treatment, a reasonable hypothesis is that longer HpPSIS treatment might further enhance the level of NGF in brain and olfactory bulbs.
Assuntos
Encéfalo/metabolismo , Fator de Crescimento Neural/biossíntese , Receptores de Fator de Crescimento Neural/biossíntese , Cloreto de Sódio/administração & dosagem , Envelhecimento/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica , Soluções Isotônicas , Fator de Crescimento Neural/genética , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Bulbo Olfatório/efeitos dos fármacos , Bulbo Olfatório/metabolismo , Pressão , Ratos , Ratos Sprague-Dawley , Receptores de Fator de Crescimento Neural/genéticaRESUMO
OBJECTIVE: Nerve growth factor (NGF) is a neurotrophin which promote and regulate the survival of neurons in the peripheral nervous system. We aimed to evaluate the nasal NGF expressions of mast cells in healthy patients after stimulation with sterilized isotonic solution delivered at high pressure. PATIENTS AND METHODS: The first part of the study was made with 21 voluntary individuals. The middle third of the inferior turbinate epithelial cells on the right nostril was scraped using a sterile curette and indicated as (pre), than a spray of sterilized isotonic solution at high pressure on the left nostril was delivered and 25 minutes later a similar stimulation was delivered on the same nostril. The stimulation was made with a specific spray. The middle third of the inferior turbinate epithelial cells on the left nostril was scraped using a sterile curette and indicated as (post). RESULTS: Forced nasal stress induced by local delivery of high pressure physiological solution causes an increase in the number of mast cells and enhances level of NGF in the nasal fluid compared to the control subjects. So based on the first part of our study, since NGF is universally known as effective in protection and repairing of neural cells damage, we started the second part and gave a treatment on the same patients, to increase NGF levels with a six months daily therapy and observed the variations in Sensorineural Hearing Loss (SNHL) and tinnitus intensity from the beginning to the end of the therapy. All patients received sterilized isotonic solution at high pressure (pression emission level: PEL): 7 g/sec for 0.5 sec (emission time: ET) in both nostrils. 25 minutes later a similar stimulation was delivered twice a day. The control group (21 pts) received normal therapy with betahistine dihydrochloride 16 mg twice a day. CONCLUSIONS: Upon acuphenometry, there was a lower intensity of tinnitus and the improvement was signaled by the patients. Patients with SNHL treated with conventional therapy had a slight worsening, while the patients treated with our new therapy which increased NGF levels, showed improvement of hearing. This new therapy represents a new therapy of SNHL, tinnitus and hearing disorders.
Assuntos
Perda Auditiva Neurossensorial/terapia , Soluções Isotônicas/administração & dosagem , Mastócitos/metabolismo , Cavidade Nasal/metabolismo , Fator de Crescimento Neural/biossíntese , Zumbido/terapia , Adulto , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/citologia , Cavidade Nasal/efeitos dos fármacos , Seios Paranasais/citologia , Seios Paranasais/efeitos dos fármacos , Seios Paranasais/metabolismo , Pressão , Zumbido/diagnósticoRESUMO
BACKGROUND: Simple snoring represents a social problem, not only because it could affect the patient's married life, but it often goes along with sleep-disordered breathing. Chronic nasal obstruction has many sequel including snoring and the inferior turbinate hypertrophy (ITH) is its most common cause. The aim of the study is to evaluate the efficacy of video-assisted endoscopic radiofrequency volumetric tissue reduction (RFVTR) to reduce snoring in patients affected by chronic nasal obstruction due to ITH. PATIENTS AND METHODS: This prospective study was conducted over 48 habitual snoring with persistent nasal obstruction due to bilateral ITH refractory to medical management received one time RFVTR of both it. Nasal symptoms were assessed both subjectively, by Visual Analog Scale (VAS) and NOSE Scale, and objectively by videorhinohygrometer. Snoring was measured by Snoring severity rated by the bed partner, in a longitudinal fashion, using VAS. All patients were evaluated pre-operatively, and after 45th day (range 35-50 days) post-operatively. RESULTS: Thirty-two subjects completed study. All patients had significant symptomatic improvement in nasal breathing (5.53 ± 2.88 vs 1.87 ± 1.75; p < 0.05), confirmed by videorhinohygrometer values (p < 0.05). We had a significantly improvement of snoring in all patients (5.62 ± 2.80 vs 1.86 ± 1.43, p < 0.001) with a mean snoring Visual Analog Scale improvement of 77.4%. CONCLUSIONS: Based on this study and literature review, it seems that RFVTR represents a safe, minimal invasive, easy performed, and time and cost effective surgery, which may decrease symptoms of snoring in patients with ITH, at least, in short-term follow-up.
Assuntos
Hipertrofia/fisiopatologia , Hipertrofia/terapia , Ronco/fisiopatologia , Ronco/terapia , Conchas Nasais/fisiopatologia , Adulto , Endoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obstrução Nasal/fisiopatologia , Obstrução Nasal/terapia , Nariz/fisiopatologia , Estudos Prospectivos , Adulto JovemRESUMO
The aim of the present study is to measure sound sensitivity of the saccule for low frequencies in a population of both young and adult prelingual deaf patients using cervical Vestibular Evoked Myogenic Potentials (cVEMPs) and to correlate the findings obtained with the phonological features. The sensitivity of the saccule to sound stimuli is well known in previous studies. The functional role of the human saccule in responding to sound stimuli is still unclear. The study was conducted on a control population of young and adults with normal hearing. The outcomes showed that the amplitude of myogenic vestibular evoked potentials resulted the most significant parameter, indicating the degree of saccular response. We found in the group of deaf adults that the saccule retained an unaltered responsiveness to sound stimuli, without suffering the age-related functional decrease as demonstrated in normal hearing patients. We assumed that the high saccular response in deaf patients is determined by a constant somatosensory stimulation (rehabilitation) of the saccule, represented by the phonetic training. We correlated the phonetic features typical of the deaf with the sensitivity of the saccule to low frequencies. Such sensitivity makes this organ the ending point of the phonetic information (perception) but also the starting point of its regulation (production). Our experience demonstrates the phonetic role of saccule in the regulation of the human voice and provides the basis for further development of this topic. Thus we strongly believe that in the deaf the saccule plays a compensatory role. The high response of the saccule allows phonemic self-regulation, compensating the low/absent tone-verbal feedback. The saccule would come rightfully to be the accessory inner ear in deaf patients. We recommend the cVEMPs in the audio-phonological assessment before starting the speech therapy or during treatment to assess the degree of responsiveness of the saccule. The resulting data would give an extremely useful information that could be ignored by the pure tone audiometry. The presence of the cVEMPs in the deaf patient may improve the expectation of the performance of speech therapy.
Assuntos
Surdez/fisiopatologia , Sáculo e Utrículo/fisiologia , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Testes de Função Vestibular/métodos , Estimulação Acústica , Adolescente , Adulto , Criança , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Fonética , Fonoterapia/métodosRESUMO
BACKGROUND: The parapharyngeal space (PPS) is a rare site for neoplasms in the head and neck and lipoma represents 0.5% of all head and neck tumors. CASE REPORT: We describe a case of a giant parapharyngeal lipoma in obese adult patient causing anatomic pharyngeal obstruction with severe obstructive sleep apnea (OSA) syndrome. The patient was successfully operated with transcervical approach. CONCLUSIONS: In patients presenting with symptoms suggestive of OSA, it is essential to rule out any physical cause and perform a comprehensive ear, nose and throat examination including fibro-endoscopic upper airway examination before referral for sleep study and management. The ideal management for OSA involves treating the underlying cause. If no definitive cause is identified, management should begin with conservative measures such as lifestyle changes and a weight loss program; if these are unsuccessful, continuous positive airway pressure (CPAP), oral appliances or upper airway surgery could be considered. Better diagnostic methods should be developed to identify the main OSA causes and improve therapeutic outcomes.