Pain-related diseases and sleep disorders

Pain and sleep share mutual relations under the influence of cognitive and neuroendocrine changes. Sleep is an important homeostatic feature and, when impaired, contributes to the development or worsening of pain-related diseases. The aim of the present review is to provide a panoramic view for the generalist physician on sleep disorders that occur in pain-related diseases within the field of Internal Medicine, such as rheumatic diseases, acute coronary syndrome, digestive diseases, cancer, and headache.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PsicobiologiaHospital Nove de Julho Centro de Dor e Neurocirurgia FuncionalUNIFESP, EPM, Depto. de PsicobiologiaSciEL

Toxicity of Corticosteroids and Biocides in Corneal Cells: Reverse Translational Research and Precision Medicine in Ophthalmology and Visual Science

INTRODUCTION: Human Corneal Epithelial Cells (HCEC) and Statens Seruminstitut Rabbit Cornea (SIRC) reproduce the cornea microenvironment in terms of epithelium and stroma, respectively. These cells are ideal for the study of the pathophysiology of the Acanthamoeba keratitis (AK) in vitro. . As there is no standartized treatment for AK, it is important to develop a study model for this condition. In addition, considerable toxicity has been reported with the use of antimicrobial compounds such as biguanides and diamidines, associated or not to corticosteroids, for the management of AK. OBJECTIVES. To study the in vitro the effect of isolated corticosteroids or associated with Polyhexamethylene Biguanide (PHMB) in a cell model of the corneal epithelium and stroma. MATERIALS AND METHODS. Cells of HCEC or SIRC were seeded into plates in the concentration of 2 x 105/mL and treated with the addition of corticosteroid (dexamethasone 0.1% or prednisolone 1.0%) or PHMB at the concentration of 0.02% or 0.04%, alone or associated with one of the above mentioned corticosteroids. Cell metabolism were quantified by fluorescence with the aid of PrestoBlueTM RESULTS. Metabolism did not differ between HCEC and SIRC after 6 hours and in the recovery period, in which cells were incubated without the chemical compounds 9 (p<0,01). The metabolic rate of recovery increased in the PHMB 0.02% plus pednisolone condition for HCEC and PHMB 0.04% plus dexamethasone for SIRC (p<0,05). Media supplemented with prednisone or dexamethasone showed to be less toxic than PHMB in any concentration, alone or in association to corticosteroids (p<0,01). DISCUSSION. The literature lacks objective data on the ocular toxicity of PHMB and / or corticosteroids in the treatment of CA. It has been demonstrated that the toxicity of PHMB is higher than that of steroids to cells of the epithelium and corneal stroma at an experimental environment, and that the combination of the two medications did not improve the condition. After removal of the drugs from the culture medium, it was observed a cellular metabolism recovery. CONCLUSIONS. This study demonstrates that the addition of corticosteroids does not change considerably the toxicity of PHMB to the corneal cells. Notwithstanding, PHMB 0.02% is preferable in cases of combined therapy for AK.Introdução. As células epiteliais da córnea (HCEC) e os fibroblastos da córnea de coelho (SIRC) reproduzem o microambiente corneano em termos de epitélio e estroma, respectivamente. Estas células são ideais para o estudo da fisiopatologia da ceratite por Acanthamoeba spp (CA) in vitro. A CA representa um importante modelo experimental, uma vez que não existe um tratamento padronizado para esta patologia e elevada toxicidade é relatada com o uso de compostos anti-microbianos, tais como biguanidas, associados ou não aos corticoides. Objetivos. Estudar o efeito in vitro de corticoides sob condição individual ou associados ao composto antimicrobiano polihexametilbiguanida (PHMB) em modelo celular de epitélio e estroma da córnea MATERIAIS E Métodos. Células HCEC ou SIRC foram semeadas em placas de ensaio na concentração de 2 x 105 / mL e tratadas com a adição de corticoides (Fosfato de Dexametasona a 0,1% ou Acetato de Prednisolona a 1,0%) e/ ou PHMB na concentração de 0,02% ou 0,04%. O metabolismo celular foi quantificado por meio da fluorescência emitida com a adição do reagente PrestoBlue®. Resultados. O metabolismo não diferiu entre as HCEC e SIRC quando comparado as 6 horas de exposição aos reagentes e o período de recuperação, em que as células foram incubadas sem os compostos químicos (p<0,01). A taxa metabólica de recuperação 7 aumentou na condição PHMB 0,02% somada a prednisolona quando aplicado às HCEC e na condição de PHMB 0,04% mais dexametasona quando aplicado às SIRC (p<0,05). Meios suplementados com prednisolona ou dexametasona demonstraram ser menos tóxicos se comparados a PHMB em qualquer concentração isolada ou em associação aos corticosteroides (p<0,01). DISCUSSÃO. A literatura carece de dados objetivos quanto a toxicidade ocular da PHMB e / ou do corticoide no tratamento da CA. Demonstrou-se em ambiente experimental que a toxicidade da PHMB é maior do que a dos corticosteróides para as células do epitélio e estroma corneano e que a combinação dos dois fármacos não melhora esta condição. Após a retirada dos medicamentos do meio de cultura, observou-se recuperação no metabolismo celular. Conclusão. O presente estudo contribui para evidenciar que a adição de corticosteróides não muda consideravelmente a toxicidade da PHMB às células da córnea. Além disso, PHMB 0,02% é preferível nos casos de terapia combinada.Dados abertos - Sucupira - Teses e dissertações (2013 a 2016

Effects of sildenafil on autonomic nervous function during sleep in obstructive sleep apnea

OBJECTIVE: To evaluate the effects of sildenafil on the autonomic nervous system in patients with severe obstructive sleep apnea. METHODS: Thirteen male patients with severe obstructive sleep apnea (mean age 43±10 years with a mean body mass index of 26.7±1.9 kg/m²) received a single 50-mg dose of sildenafil or a placebo at bedtime. All-night polysomnography and heart rate variability were recorded. Frequency domain analysis of heart rate variability was performed for the central five-minute sample of the longest uninterrupted interval of slow wave and rapid eye movement sleep, as well as for one-minute samples during apnea and during slow wave and rapid eye movement sleep after resumption of respiration. RESULTS: Compared to the placebo, sildenafil was associated with an increase in the normalized high-frequency (HFnu) components and a decrease in the low/high-frequency components of the heart rate variability ratio (LF/HF) in slow wave sleep (p<0.01 for both). Differences in heart rate variability parameters between one-minute post-apnea and apnea samples (&#916;= difference between resumption of respiration and apnea) were assessed. A trend toward a decreasing magnitude of &#916;LF activity was observed during rapid eye movement sleep with sildenafil in comparison to placebo (p=0.046). Additionally, &#916; LF/HF in SWS and rapid eye movement sleep was correlated with mean desaturation (sR= -0.72 and -0.51, respectively, p= 0.01 for both), and &#916; HFnu in rapid eye movement sleep was correlated with mean desaturation (sR= 0.66, p= 0.02) and the desaturation index (sR= 0.58, p = 0.047). CONCLUSIONS: The decrease in arousal response to apnea/hypopnea events along with the increase in HFnu components and decrease in LH/HF components of the heart rate variability ratio during slow wave sleep suggest that, in addition to worsening sleep apnea, sildenafil has potentially immediate cardiac effects in patients with severe obstructive sleep apnea

Herpes zoster ophthalmicus and varicella zoster virus vasculopathy

Herpes zoster (HZ) corresponds to the reactivation of varicella zoster virus (VZV). Among adults, the ophthalmic division of the trigeminal nerve is one of the most common sites of involvement. Vasculopathy caused by HZ is associated with significant morbidity and mortality, affecting structures such as the brain, which can lead to stroke. In this review, we analyzed the epidemiological and clinical aspects of the vascular involvement of VZV, focusing on the peculiarities of its association with ocular HZ. A review of the available literature indicated that ocular involvement of HZ was a risk factor for vasculopathy after adjusting for age, sex, body mass index, smoking, indicators of metabolic syndrome, and vascular and heart diseases. Considering the severity of this complication, vascular disease mediated by VZV requires early diagnosis and aggressive treatment. Finally, the anti-HZ vaccine has been recommended as a prophylactic measure in the elderly, but it should be used with caution in immunocompromised individuals.Univ Fed Sao Paulo UNIFESP, EPM, Dept Ophthalmol & Visual Sci, Sao Paulo, SP, BrazilSoc Brasileira Imunizacao, Sao Paulo, SP, BrazilInst Visao, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Dept Ophthalmol & Visual Sci, Sao Paulo, SP, BrazilWeb of Scienc

Relationship between Daytime Sleepiness and Intrinsically Photosensitive Retinal Ganglion Cells in Glaucomatous Disease

Patients with glaucoma showed to have higher daytime sleepiness measured by Epworth sleepiness scale. In addition, this symptom was associated with pupillary reflex and polysomnography parameters. These ipRGC functions might be impaired in patients with glaucoma, leading to worse quality of life

External factors related to hand dexterity analyzed by an ophthalmic microsurgical simulator: principles for improving skills in vitreoretinal surgery

Objective. Study 1: to assess the novice vitreoretinal surgeons’ performance after combined caffeine and β-blocker (propranolol) exposure. Study 2: to analyze the novice vitreoretinal surgeons’ performance after caffeine, propranolol, alcohol, exercise, or sleep deprivation, separately. Study 3: to study the fine motor deficiencies of chronic cocaine users (CCU). Methods. Studies 1 and 2 included 15 vitreoretinal surgeons with <2 years of surgical experience. Performance was assessed using the Eyesi simulator after the following exposures. Study 1- day 1: placebo, caffeine (2.5mg/kg, additional 2.5mg/kg), and propranolol (0.6mg/kg); day 2: placebo, propranolol (0.2mg/kg, additional 0.4mg/kg), and caffeine (5.0mg/kg). Study 2- day 1: placebo and caffeine (2.5mg/kg, additional 2.5mg/kg); day 2: placebo, propranolol (0.2mg/kg, additional 0.4mg/kg); day 3: baseline, breathalyzer reading of 0.06%-0.10% and 0.11%-0.15% blood alcohol concentration (BAC); day 4: push-up sets with 50% and 85% repetition maximum; day 5: 3-hour sleep deprivation. Performance variations related to placebo or baseline were calculated (∆). Study 3- we recruited 24 nonphysician CCU and 24 sex-/age-matched non-physician controls to assess the fine dexterity using the Eyesi simulator. The outcomes included surgical score (0–100, worst-best), task completion time (minutes), intraocular trajectory (mm), and tremorspecific score (0-100, worst-best). Results. Study 1: post-caffeine treatment with propranolol 0.6mg/kg was associated with performance improvement; however, the performance remained inferior compared with propranolol 0.2mg/kg alone for total score (570.0 vs. 617.0, P=0.01), tremor-specific score (50.0 vs. 75.0, P=0.03), trajectory (2,265.9 vs. 2,080.7mm, P=0.03), and time (14.9 vs. 12.7min; P=0.048). Study 2: performances worsened with increasing alcohol exposure in score (X2=7, df=2, P=0.03) and trajectory (X2=6.86, df=2, P=0.03). BAC-1 (0.06%-0.10%) and BAC- 2 (0.11%-0.15%) worsened performance compared with improvements after propranolol-1 (0.2mg/kg) and propranolol-2 (0.6mg/kg) in score (∆BAC-1=-22 vs. ∆propranolol-2=+13, P=0.02; ∆BAC-2=-43 vs. ∆propranolol-1=+23, P=0.01), tremor score (∆BAC- 1=-7.5 vs. ∆propranolol-2=+5, P=0.008; ∆BAC-2=-15 vs. ∆propranolol-1=+8, P=0.009), and time (∆BAC-1=-0.05min vs. ∆propranolol-2=-1.35min, P=0.008; ∆BAC-2=+0.46min vs. ∆propranolol-1=- 0.83min, P=0.009). Trajectory was negatively affected by 0.11%-0.15%BAC compared to 0.2mg/kg propranolol (∆BAC-2=+204.84mm vs. ∆propranolol-1=-221.7mm, P=0.006). Propranolol 0.6mg/kg positively affected score compared to deterioration after 2.5mg/kg caffeine (∆propranolol-2=+7 vs. ∆caffeine=-13, P=0.03). Although 2.5mg/kg caffeine positively affected time (∆caffeine=-0.71min vs. ∆BAC-2=+0.46min, P=0.009) and trajectory (∆caffeine=-78.7mm vs. ∆BAC-2=+204.8mm, P=0.008) compared to 0.11%-0.15%BAC, score decreased after caffeine compared to baseline performance. Study 3: score was lower among CCU compared to controls for bimanual tasks (4.50±14.30 vs. 18.46±26.64, P=0.012), for exercises demanding upper-lower limb coordination (74.13±35.01 vs. 85.21±24.1, P=0.045), and for total score (27.38±15.06 vs. 39.5±18.66, P=0.021). CCU took longer when performing exercises demanding upperlower limb coordination compared to controls (1.26±0.38 vs. 1.02±0.44min, P=0.006). Individuals who used cocaine during the previous month had an independently lower bimanual score compared to controls (1.42±4.91 vs. 18.46±26.64, P=0.018). Conclusion. Study 1: performance after propranolol alone was better than after propranolol and caffeine combined. Study 2: alcohol diminished performance in a dose-dependent manner. Caffeine 2.5mg/kg negatively affected dexterity, and propranolol 0.2mg/kg improved performance. No changes in performance were observed after physical exercise or 3-hour sleep deprivation. Study 3: chronic cocaine abuse negatively impacted fine dexterity as measured by bimanual tasks or maneuvers that required upper-lower limb coordination.Objetivo. Estudo 1: avaliar o desempenho de cirurgiões vitreorretinianos novatos após exposição combinada à cafeína com β-bloqueador (propranolol). Estudo 2: analisar o desempenho dos mesmos cirurgiões após cafeína, propranolol, álcool, exercício ou privação de sono, separadamente. Estudo 3: estudar a deficiência na motricidade fina de usuários crônicos de cocaína (UCC). Métodos. Nos estudos 1 e 2, incluímos 15 cirurgiões vitreorretinianos com <2 anos de experiência cirúrgica. O simulador Eyesi avaliou o desempenho após as seguintes exposições. Estudo 1- dia 1: placebo, cafeína (2,5mg/kg, 2,5mg/kg adicional) e propranolol (0,6mg/kg); dia 2: placebo, propranolol (0,2mg/kg, 0,4mg/kg adicional) e cafeína (5,0mg/kg). Estudo 2- dia 1: placebo, cafeína (2,5mg/kg, 2,5mg/kg adicional); dia 2: placebo, propranolol (0,2mg/kg, 0,4mg/kg adicional); dia 3: concentração alcoólica sanguínea (CAS) de 0,06-0,10% e 0,11-0,15%; dia 4: flexões com 50% e 85% da repetição máxima; dia 5: privação de sono. Calculou-se a variação de desempenho relacionada ao placebo ou à simulação basal (∆). Estudo 3- recrutou-se 24 UCC não médicos e 24 controles não médicos para avaliar a destreza usando o simulador Eyesi. Os resultados incluíram pontuações cirúrgicas (0-100, pior-melhor), tempo de conclusão da tarefa (minutos), trajetória intraocular (mm) e pontuação tremor-específica (0-100, pior-melhor). Resultados. Estudo 1: Tratamento pós-cafeína com propranolol 0,6mg/kg aprimorou o desempenho; entretanto, a destreza permaneceu inferior comparado ao propranolol 0,2mg/kg isolado para pontuação total (570.0 vs. 617.0, P=0.01), pontuação tremorespecífica (50.0 vs. 75.0, P=0.03), trajetória (2265.9 vs. 2080.7mm, P=0.03) e tempo (14.9 vs. 12.7min; P=0.048). Estudo 2: após exposição alcoólica progressiva, o desempenho piorou na pontuação (X2=7, gl=2, P=0,03) e trajetória (X2=6,86, gl=2, P=0,03). A CAS-1 (0,06%-0,10%) e a CAS-2 (0,11%-0,15%) comprometeram o desempenho comparado à melhoria após propranolol-1 (0.2mg/kg) e propranolol-2 (0,6mg/kg) na pontuação (∆CAS-1=-22 vs. ∆Propranolol-2=+13, P=0,02; ∆CAS-2=-43 vs. ∆Propranolol-1=+23, P=0,01), pontuação tremor-específica (∆CAS-1=-7,5 vs. ∆Propranolol-2=+5, P=0,008; ∆CAS-2=-15 vs. ∆Propranolol-1=+8, P=0,009) e tempo (∆CAS-1=-0,05min vs. ∆Propranolol-2=-1,35min, P=0,008; ∆CAS-2=+0,46min vs. ∆Propranolol-1=-0,83min, P=0,009). A trajetória aumentou com 0,11-0,15%CAS comparado ao propranolol 0,2mg/kg (∆CAS- 2=+204,84mm vs. ∆Propranolol-1=-221,7mm, P=0,006). Propranolol 0,6mg/kg otimizou a pontuação comparado à deterioração após cafeína 2,5mg/kg (∆Propranolol-2=+7 vs. ∆Cafeína=-13, P=0,03). A cafeína 2,5mg/kg diminuiu o tempo (∆Cafeína=-0,71min vs. ∆CAS- 2=+0,46min, P=0,009) e a trajetória (∆CAFEÍNA=-78,7mm vs. ∆CAS-2=+204,8mm, P=0,008) comparado a 0,11%-0,15%CAS, entretanto a pontuação diminuiu após a cafeína comparado a performance basal. Estudo 3: a pontuação diminuiu entre UCC comparado aos controles para tarefas bimanuais (4,50±14,30 vs. 18,46±26,64, P=0,012), exercícios dos membros superiores com inferiores (74,13±35,01 vs. 85,21±24,1, P=0,045) e para a pontuação total (27,38±15,06 vs. 39,5±18,66, P=0,021). UCC demoraram mais em exercícios dos membros superiores com inferiores comparado aos controles (1,26±0,38 vs. 1,02±0,44min, P=0,006). Indivíduos que usaram cocaína no último mês tiveram pontuação bimanual inferior comparado aos controles (1,42±4,91 vs. 18,46±26,64, P=0,018). Conclusão. Estudo 1: propranolol isolado melhorou a performance comparado à combinação de propranolol com cafeína. Estudo 2: álcool diminuiu o desempenho dose-dependentemente. Cafeína 2,5mg/kg deteriorou a destreza e propranolol 0,2mg/kg melhorou o desempenho. Não ocorreu mudanças após exercício ou privação de sono. Estudo 3: o uso crônico de cocaína prejudicou a destreza em tarefas bimanuais ou que exigiam coordenação dos membros superiores e inferiores.Dados abertos - Sucupira - Teses e dissertações (2021

The Question of a Role for Statins in Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in patients over the age of 65 years in industrialized countries. Epidemiologic studies suggest that high dietary fat intake is a risk factor for the development and progression of both vascular and retinal disease. These, and other associations, suggest a hypothesis linking elevated cholesterol and AMD progression. It follows, therefore, that cholesterol-lowering medications, such as statins, may influence the onset and progression of AMD. However, the findings have been inconclusive as to whether statins play a role in AMD. Due to the significant public health implications of a potential inhibitory effect of statins on the onset and progression of AMD, it is important to continually evaluate emerging findings germane to this question