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1.
Braz J Psychiatry ; 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-37994832

ABSTRACT

OBJECTIVE: Schizophrenia (SCZ) is a disabling disorder that continues to defy clinicians and researchers. We investigated the effects of sodium nitroprusside (sNP) in an animal model of SCZ and as an add-on therapy in patients and the relationship between treatment with sNP and activity of the nDel1 enzyme, whose involvement in the pathophysiology of the disorder has been suggested earlier. METHODS: Ndel1 activity was measured following sNP infusions in spontaneously hypertensive rats (SHR; 2.5 or 5.0 mg/kg) and in a double-blind trial with SCZ patients (0.5 µg/kg/min). RESULTS: Ndel1 activity was significantly reduced after sNP infusion in blood of SHR compared to controls, and in patients receiving sNP (t = 7.756, df = 97, p < 0.0001, dcohen = 1.44) compared to placebo. Reduced Ndel1 activity between baseline and the end of the infusion was only seen in patients after treatment with sNP. CONCLUSION: Our findings suggest that SCZ patients may benefit from adjunctive therapy with sNP and that the Ndel1 enzyme is a candidate biomarker of psychopathology in the disorder. Future research should look into the role of Ndel1 in SCZ and the potential effects of sNP and drugs with similar profiles of action in both animals and patients.

2.
Br J Ophthalmol ; 107(10): 1502-1508, 2023 10.
Article in English | MEDLINE | ID: mdl-35840291

ABSTRACT

BACKGROUND: The ILUVIEN Registry Safety Study was a multicentre, open-label, non-randomised, observational, phase 4 study designed to assess the safety and effectiveness of the fluocinolone acetonide (FAc) implant in all indications in real-world practices in Europe. METHODS: The study included data collected prospectively and retrospectively. Patients receiving FAc implants between 2013 and 2017 were included and monitored until the last patient reached ≥3 years of follow-up. Mean intraocular pressure (IOP) data over the course of the study, along with IOP events, use of IOP-lowering therapy, mean change in visual acuity (VA) and information on supplemental therapy use were analysed post-FAc implantation. RESULTS: Six hundred and ninety-five eyes from 556 patients, with a mean±SD follow-up of 1150.5±357.36 days, were treated with a FAc implant. 96.7% of eyes had chronic diabetic macular oedema (cDMO). IOP lowering was achieved in 34.5% of eyes using topical agents and 4.3% by surgery. Seventy-three eyes (64.6% of 113 phakic) required cataract surgery during follow-up. Mean VA increased from a baseline of 52.2 letters to 57.1 letters at month 36, with improvement observed up to month 48. Supplementary therapies were given in 43.7% of eyes. When classified by length of cDMO less than or greater than the median duration those with a shorter history experienced greater VA gains than those with a longer history. CONCLUSION: This study confirms the favourable, long-term benefit-to-risk profile of the FAc implant in eyes with cDMO, with an additional benefit in patients when this therapy is administered earlier.


Subject(s)
Diabetic Retinopathy , Macular Edema , Humans , Fluocinolone Acetonide , Glucocorticoids/therapeutic use , Macular Edema/drug therapy , Retrospective Studies , Drug Implants , Intravitreal Injections , Iris
3.
Cell Mol Life Sci ; 80(1): 22, 2022 Dec 31.
Article in English | MEDLINE | ID: mdl-36585968

ABSTRACT

Proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and neovascular age-related macular degeneration (nAMD) are among the leading causes of blindness. Due to the multifactorial nature of these vitreoretinal diseases, omics approaches are essential for a deeper understanding of the pathophysiologic processes underlying the evolution to a proliferative or neovascular etiology, in which patients suffer from an abrupt loss of vision. For many years, it was thought that the function of the vitreous was merely structural, supporting and protecting the surrounding ocular tissues. Proteomics studies proved that vitreous is more complex and biologically active than initially thought, and its changes reflect the physiological and pathological state of the eye. The vitreous is the scenario of a complex interplay between inflammation, fibrosis, oxidative stress, neurodegeneration, and extracellular matrix remodeling. Vitreous proteome not only reflects the pathological events that occur in the retina, but the changes in the vitreous itself play a central role in the onset and progression of vitreoretinal diseases. Therefore, this review offers an overview of the studies on the vitreous proteome that could help to elucidate some of the pathological mechanisms underlying proliferative and/or neovascular vitreoretinal diseases and to find new potential pharmaceutical targets.


Subject(s)
Diabetic Retinopathy , Vitreoretinopathy, Proliferative , Humans , Vitreous Body/pathology , Proteome , Vitreoretinopathy, Proliferative/genetics , Vitreoretinopathy, Proliferative/pathology , Retina/pathology , Diabetic Retinopathy/genetics , Diabetic Retinopathy/pathology
4.
Antioxidants (Basel) ; 11(3)2022 Mar 06.
Article in English | MEDLINE | ID: mdl-35326156

ABSTRACT

Oxidative stress is defined as an unbalance between pro-oxidants and antioxidants, as evidenced by an increase in reactive oxygen and reactive nitrogen species production over time. It is important in the pathophysiology of retinal disorders such as diabetic retinopathy, age-related macular degeneration, retinal detachment, and proliferative vitreoretinopathy, which are the focus of this article. Although the human organism's defense mechanisms correct autoxidation caused by endogenous or exogenous factors, this may be insufficient, causing an imbalance in favor of excessive ROS production or a weakening of the endogenous antioxidant system, resulting in molecular and cellular damage. Furthermore, modern lifestyles and environmental factors contribute to increased chemical exposure and stress induction, resulting in oxidative stress. In this review, we discuss the current information about oxidative stress and the vitreous proteome with a special focus on vitreoretinal diseases. Additionally, we explore therapies using antioxidants in an attempt to rescue the body from oxidation, restore balance, and maximize healthy body function, as well as new investigational therapies that have shown significant therapeutic potential in preclinical studies and clinical trial outcomes, along with their goals and strategic approaches to combat oxidative stress.

5.
J Clin Psychopharmacol ; 41(3): 260-266, 2021.
Article in English | MEDLINE | ID: mdl-33857028

ABSTRACT

BACKGROUND: Schizophrenia is a complex disabling mental disorder, and many patients present poor response to available treatments. Accumulating evidence about the role of the glutamate/nitric oxide pathway in mediating the positive and negative symptoms of schizophrenia suggests potential benefits of drugs that modulate this system. The aim of this study was to test the efficacy of isosorbide mononitrate (ISMN) as an adjunctive therapy for symptomatic outpatients with schizophrenia. METHODS: This was a 2-month randomized, double-blind, placebo-controlled trial with 24 schizophrenia patients. Participants were treated with ISMN 50 mg for 1 month and placebo for another month in a crossover design. The Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, Global Assessment of Functioning, and MATRICS Cognitive Consensual Battery were used for symptom assessment and arterial spin labeling was used to assess brain activation patterns. RESULTS: We found significant differences in the total, general, and positive subscales of the PANSS, Global Assessment of Functioning scores, and Clinical Global Impression scores during treatment with ISMN relative to placebo. No treatment effects were found comparing scores in the MATRICS Cognitive Consensual Battery and the negative subscale of the PANSS between the active and placebo conditions. A post hoc analysis of neuroimaging data showed reduced activity in the thalamus in subgroup of patients with severe psychopathology. CONCLUSIONS: Schizophrenia patients with persistent symptoms showed significant improvement after 4 weeks of treatment with ISMN 50 mg/d compared with placebo. Isosorbide mononitrate added beneficial effects to antipsychotic treatment in terms of positive symptoms and functioning.


Subject(s)
Antipsychotic Agents/administration & dosage , Isosorbide Dinitrate/analogs & derivatives , Schizophrenia/drug therapy , Adult , Cross-Over Studies , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Isosorbide Dinitrate/administration & dosage , Male , Psychiatric Status Rating Scales , Schizophrenia/physiopathology , Treatment Outcome , Vasodilator Agents/administration & dosage
6.
Trends psychiatry psychother. (Impr.) ; 42(3): 262-266, July-Sept. 2020. tab
Article in English | LILACS | ID: biblio-1139839

ABSTRACT

Abstract Introduction The Internet Gaming Disorder Scale - Short Form (IGDS9-SF) assesses the severity, harmful effects and/or consequences of excessive online and offline gaming. Its conciseness and theoretical foundations on current diagnostic criteria of gaming disorders make it a useful resource for clinical and screening settings. Objective To describe the process of cross-cultural adaptation of the IGDS9-SF to the Brazilian context. Methods The cross-cultural adaptation involved the steps of independent translation of the instrument, synthesis version, back-translation, pre-test and elaboration of the final version. Content validity assessment was conducted by a multidisciplinary committee of experts and consisted of both a quantitative analysis (calculation of content validity coefficients - CVC) and a qualitative analysis (assessment of the experts' comments and suggestions). The pre-test sample consisted of 30 gamers with variable sociodemographic characteristics. Results The cross-cultural adaptation of the scale followed the proposed protocol, and the CVC was satisfactory (≥ 0.83) for all the structures and equivalences assessed. Most of the suggestions made by the experts were accepted (mainly adjustments and language standardization). The gamers who participated in the pre-test judged the scale easy to understand and did not suggest changes. Discussion The Brazilian version of the IGDS9-SF showed adequate content validity and is available for researchers and clinicians, as well as for the investigation of additional psychometric characteristics.


Subject(s)
Adult , Humans , Psychiatric Status Rating Scales , Psychometrics/methods , Video Games , Internet Addiction Disorder/diagnosis , Psychiatric Status Rating Scales/standards , Psychometrics/standards , Brazil
7.
Trends Psychiatry Psychother ; 42(3): 262-266, 2020.
Article in English | MEDLINE | ID: mdl-32844978

ABSTRACT

INTRODUCTION: The Internet Gaming Disorder Scale - Short Form (IGDS9-SF) assesses the severity, harmful effects and/or consequences of excessive online and offline gaming. Its conciseness and theoretical foundations on current diagnostic criteria of gaming disorders make it a useful resource for clinical and screening settings. OBJECTIVE: To describe the process of cross-cultural adaptation of the IGDS9-SF to the Brazilian context. METHODS: The cross-cultural adaptation involved the steps of independent translation of the instrument, synthesis version, back-translation, pre-test and elaboration of the final version. Content validity assessment was conducted by a multidisciplinary committee of experts and consisted of both a quantitative analysis (calculation of content validity coefficients - CVC) and a qualitative analysis (assessment of the experts' comments and suggestions). The pre-test sample consisted of 30 gamers with variable sociodemographic characteristics. RESULTS: The cross-cultural adaptation of the scale followed the proposed protocol, and the CVC was satisfactory (≥ 0.83) for all the structures and equivalences assessed. Most of the suggestions made by the experts were accepted (mainly adjustments and language standardization). The gamers who participated in the pre-test judged the scale easy to understand and did not suggest changes. DISCUSSION: The Brazilian version of the IGDS9-SF showed adequate content validity and is available for researchers and clinicians, as well as for the investigation of additional psychometric characteristics.


Subject(s)
Internet Addiction Disorder/diagnosis , Psychiatric Status Rating Scales , Psychometrics/methods , Video Games , Adult , Brazil , Humans , Psychiatric Status Rating Scales/standards , Psychometrics/standards
8.
Arch. Clin. Psychiatry (Impr.) ; 47(4): 110-118, July-Aug. 2020. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1130992

ABSTRACT

Abstract Background Posttraumatic stress disorder consists of a set of symptoms that occurs in response to one or more traumatic events and can occur in postpartum, from traumatic situations related to the birth or to the baby's health in the first days of life. It is important tracking the presence of birth trauma, but there is not available instruments in the Brazilian context for this purpose. Objectives To present the cross-cultural adaptation of City Birth Trauma Scale (BiTS) into Brazilian portuguese. Methods Cross-cultural adaptation involved independent translations, synthesis,back-translation, and submission to the original author's appreciation. After the scale was subjected to face validity, followed by a pilot study with postpartum mothers. Results All steps were performed for the cross-cultural adaptation. Regarding face validity, items evaluated concerning different types of equivalence, presented satisfactory agreement values (≥4.20). Most of the expert's suggestions were followed, being the main ones related to adjustments in prepositions, pronouns and verbal subjects. Pilot study showed that the mothers had been able to understand and respond to the instrument without adjustments. Discussion BiTS's Brazilian version proved to be cross-culturally adapted, ensuring the possibility of intercultural data comparison from the semantic, idiomatic, cultural, and conceptual perspectives. New studies are being conducted to attest its psychometric adequacy.

9.
Eur J Psychotraumatol ; 11(1): 1720336, 2020.
Article in English | MEDLINE | ID: mdl-32128046

ABSTRACT

Background: Adverse childhood experiences (ACE) affect physical and mental health and may appear as risk factors for the development of different conditions in adult life. Objective: To perform a literature review and meta-analysis on risk indicators for the development of chronic lung diseases in adulthood associated with ACE. Method: We conducted a systematic literature review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the online databases PubMed, PsycINFO, and Web of Science. Quantitative studies involving male and female adults were included. Fixed- and random-effect models were used in the estimation of meta-analytical measures. The heterogeneity between studies was assessed using I2 statistics and Cochran's Q test. Results: A total of 19 studies were selected for the meta-analysis. The analyses showed statistically significant associations between ACE and lung diseases in general (OR = 1.41; CI 95%: 1.28-1.54), besides specific associations with asthma (OR = 1.32; CI 95%: 1.13-1.50) and COPD (OR = 1.44; CI 95%: 1.13-1.76). When the mediating effect of smoking was assessed separately we found a significant - although not quite expressive - association (OR = 1.06; CI 95%: 1.02 to 1.10), which weakens the hypothesis that a direct relationship exists between childhood trauma and the occurrence of lung diseases. Conclusions: ACE are an important risk factor for the development of lung diseases in adulthood, whether through direct or indirect contribution to this outcome, which highlights the relevance of increasing the awareness of health staff for the early detection and intervention in situations of vulnerability or risk in childhood as an important preventative measure.


Antecedentes: Experiencias infantiles adversas (ACE) afectan la salud física y mental y pueden aparecer como factores de riesgo para el desarrollo de diferentes afecciones en la vida adulta.Objetivo: realizar una revisión de la literatura y un metanálisis sobre indicadores de riesgo para el desarrollo de enfermedades pulmonares crónicas en la edad adulta asociadas con ACE.Método: Realizamos una revisión sistemática de la literatura de acuerdo con las pautas PRISMA (Elementos de Referencia para Revisiones Sistemáticas y Metaanálisis) utilizando las bases de datos en línea PubMed, PsycINFO y Web of Science. Se incluyeron estudios cuantitativos con hombres y mujeres adultos. Se utilizaron modelos de efectos fijos y aleatorios en la estimación de medidas meta-analíticas. La heterogeneidad entre los estudios se evaluó mediante estadísticas I 2 y la prueba Q de Cochran.Resultados: Se seleccionaron un total de 19 estudios para el metanálisis. Los análisis mostraron asociaciones estadísticamente significativas entre el ACE y las enfermedades pulmonares en general (OR = 1.41; IC 95%: 1.28­1.54), además de asociaciones específicas con el asma (OR = 1.32; IC 95%: 1.13 ­ 1.50) y EPOC (OR = 1,44; IC 95%: 1,13­1,76). Cuando el efecto mediador del tabaquismo se evaluó por separado, encontramos una asociación significativa (aunque no del todo clara) (OR = 1.06; IC 95%: 1.02 a 1.10), lo que debilita la hipótesis de que existe una relación directa entre el trauma infantil y la ocurrencia de enfermedades pulmonares.Conclusiónes: las experiencias ACE son un factor de riesgo importante para el desarrollo de enfermedades pulmonares en la edad adulta, ya sea a través de una contribución directa o indirecta, lo que resalta la relevancia de aumentar la conciencia del personal de salud para la detección temprana y la intervención en situaciones de vulnerabilidad o riesgo en la infancia como una medida preventiva importante.

10.
Curr Opin Psychiatry ; 33(3): 250-254, 2020 05.
Article in English | MEDLINE | ID: mdl-32068568

ABSTRACT

PURPOSE OF REVIEW: The two past decades have seen the production of a vast amount of evidence about the genetic and nongenetic factors that contribute to the onset of psychosis from various fields of research. The present article reviews recent evidence from four of these fields that were shown to be strongly associated with psychosis: proneness, urbanicity, trauma, and cannabis use. RECENT FINDINGS: The evidence reviewed shows that all four sets of factors investigated here are implicated in the occurrence of psychosis. The specificity and complexity of these associations, however, are not yet clear and recent findings show that the directions of the associations described may be different than we first thought. SUMMARY: It is clear that psychosis is strongly affected by a number of environmental determinants that act in concert with genetic determinants to cause psychotic disorders; however, these influences are complex and their actual impact may be difficult to establish because of poor definitions and specificity. Urbanicity in special is a poorly defined concept that seems to encompass different sets of factors in each study, which hinders discussions and conclusions regarding its impact.


Subject(s)
Cannabis/adverse effects , Psychotic Disorders/etiology , Urban Population , Humans , Precipitating Factors , Psychotic Disorders/epidemiology , Risk Factors
11.
Ophthalmic Res ; 63(2): 114-121, 2020.
Article in English | MEDLINE | ID: mdl-31801148

ABSTRACT

BACKGROUND: First-line treatment for diabetic macular edema (DME) is usually with antivascular endothelial growth factor agents, followed by intravitreal corticosteroids as a second-line treatment option. Long-term corticosteroids may offer quality of life and effectiveness benefits over short-term implants. OBJECTIVES: To evaluate outcomes of patients with persistent or recurrent DME who switched from a short-term (dexamethasone) to a long-term (fluocinolone acetonide, FAc) corticosteroid intravitreal implant in a real-world setting. METHODS: This is a retrospective study in 9 Portuguese centers. An FAc intravitreal implant was administered according to product labeling. Effectiveness outcomes were mean change in visual acuity (VA; ETDRS letters), central retinal thickness (CRT; µm), and macular volume (MV; mm3). The safety outcome was mean change in intraocular pressure (IOP; mm Hg). All were analyzed at months 1 and 3, and then quarterly until month 24 after implantation. RESULTS: Forty-four eyes from 36 patients were analyzed. Mean duration of DME was 3.3 ± 1.9 years, and mean follow-up was 8 months. From baseline following FAc implantation, VA increased significantly at months 1 and 6 (mean +6.82 and +13.02 letters, respectively; p = 0.005), and last observation carried forward (LOCF; mean +8.3 letters; p = 0.002). CRT improved significantly at months 1 and 6 (mean -71.81 and -170.77 µm, respectively; p = 0.001), and LOCF (mean -121.46 µm; p = 0.001). MV was consistently, but not significantly, decreased from baseline to LOCF (mean -0.69 mm3; p = 0.062). The mean change in IOP was -0.25 and +0.88 mm Hg at months 1 and 6, respectively (p = 0.268), and +1.86 mm Hg at LOCF (p = 0.036). Increases were controlled with topical medication in most cases. CONCLUSIONS: The FAc intravitreal implant is effective in patients previously treated with short-term corticosteroid implants. Thus, after a suboptimal response to antiangiogenics or a short-term corticosteroid, a single FAc implant may be considered an effective and tolerable treatment that can improve long-term outcomes for patients with sight-threatening DME.


Subject(s)
Diabetic Retinopathy/drug therapy , Fluocinolone Acetonide/administration & dosage , Macular Edema/drug therapy , Visual Acuity , Aged , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Drug Implants , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , Humans , Intraocular Pressure/drug effects , Intravitreal Injections , Macula Lutea/pathology , Macular Edema/diagnosis , Macular Edema/etiology , Male , Quality of Life , Retrospective Studies , Time Factors , Treatment Outcome
12.
Psychiatry Clin Neurosci ; 73(12): 754-760, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31490607

ABSTRACT

AIM: The Structured Clinical Interview for the DSM is one of the most used diagnostic instruments in clinical research worldwide. The current Clinician Version of the instrument (SCID-5-CV) has not yet been assessed in respect to its psychometric qualities. We aimed to assess the clinical validity and different reliability indicators (interrater test-retest, joint interview, face-to-face vs telephone application) of the SCID-5-CV in a large sample of 180 non-prototypical and psychiatric patients based on interviews conducted by raters with different levels of clinical experience. METHODS: The SCID-5-CV was administered face-to-face and by telephone by 12 psychiatrists/psychologists who took turns as raters and observers. Clinical diagnoses were established according to DSM-5 criteria and the longitudinal, expert, all data (LEAD) procedure. We calculated the percentage of agreement, diagnostic sensitivity and specificity, and the level of agreement (kappa) for diagnostic categories and specific diagnoses. RESULTS: The percentage of positive agreement between the interview and clinical diagnoses ranged between 73% and 97% and the diagnostic sensitivity/specificity were >0.70. In the joint interview, the levels of positive agreement were high (>75%) and kappa levels were >0.70 for most diagnoses. The values were less expressive, but still adequate, for interrater test-retest interviews. CONCLUSION: The SCID-5-CV presented excellent reliability and high specificity as assessed with different methods. The clinical validity of the instrument was also confirmed, which supports its use in daily clinical practice. We highlight the adequacy of the instrument to be used via telephone and the need for careful use by professionals with little experience in psychiatric clinical practice.


Subject(s)
Diagnostic and Statistical Manual of Mental Disorders , Mental Disorders/diagnosis , Psychiatric Status Rating Scales/statistics & numerical data , Reproducibility of Results , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Interview, Psychological/methods , Male , Middle Aged , Observer Variation , Psychometrics , Sensitivity and Specificity , Young Adult
13.
Br J Ophthalmol ; 103(8): 1072-1077, 2019 08.
Article in English | MEDLINE | ID: mdl-30242062

ABSTRACT

AIMS: The ILUVIEN Registry Safety Study is an ongoing, multicentre, open-label, observational study collecting real-world data on the safety and effectiveness of the 0.2 µg/day fluocinolone acetonide (FAc) implant in patients treated according to the European label requirements. METHODS: Patients included in this analysis were treated for the licensed indication of chronic diabetic macular oedema (cDMO; that is, DMO that persists or recurs despite treatment). Data presented in the current analysis were collected from patient records up to 6 March 2017. Visual acuity (VA) data, including mean change in VA over time and at last observation, intraocular pressure (IOP) over the course of the study, IOP events, use of IOP-lowering therapy and cup:disc ratio were analysed. Information on additional DMO treatments post-FAc implant was also captured. RESULTS: Five hundred and sixty-three patients (593 eyes) were enrolled on the study. Mean IOP for the overall population remained within the normal range throughout follow-up and 76.7% of patients did not require IOP-lowering therapy following treatment with the FAc implant. Sixty-nine per cent of eyes did not require additional DMO treatments. Mean VA in the overall population increased from 51.9 letters at baseline to 55.6 letters at month 12, with a significant increase of 2.9 letters at last observation. Patients with short-term cDMO experienced greater VA gains than those with long-term cDMO. CONCLUSIONS: The results of this analysis are comparable with those of other studies, including the Fluocinolone Acetate for Macular Edema study. The study reinforces the good safety and effectiveness profile of FAc, and demonstrates the benefit of early FAc treatment.


Subject(s)
Diabetic Retinopathy/drug therapy , Fluocinolone Acetonide/administration & dosage , Intraocular Pressure/physiology , Macular Edema/drug therapy , Visual Acuity , Aged , Diabetic Retinopathy/complications , Diabetic Retinopathy/physiopathology , Drug Implants , Europe , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , Humans , Intraocular Pressure/drug effects , Intravitreal Injections , Macular Edema/etiology , Macular Edema/physiopathology , Male , Middle Aged , Retrospective Studies , Treatment Outcome
14.
Growth Factors ; 36(1-2): 48-57, 2018 04.
Article in English | MEDLINE | ID: mdl-29969324

ABSTRACT

VEGF-A and VEGF-B are proangiogenic and key regulating factors for blood vessel growth. This study aims to compare VEGF-A and VEGF-B levels in the serum and vitreous of patients with neovascular pathology versus non-neovascular pathology. Our findings showed vitreous VEGF-A and VEGF-B levels increased in patients with neovascular disease, with higher levels of VEGF-A compared to VEGF-B (p ≤ .05). In the diabetic retinopathy (DR) group, higher vitreous VEGF-A or VEGF-B were found in proliferative diabetic retinopathy (PDR) than in non-PDR. The strong correlation between VEGF-A and VEGF-B demonstrates a simultaneous pathological increase of cytokines (p < .001), suggesting besides VEGF-A, VEGF-B is another contributor to ocular pathologies involving angiogenesis. There was no correlation between vitreous and serum VEGF-A or VEGF-B; however, a correlation between vitreous (VEGF-A or VEGF-B) and macular volume (p < .05) in DR patients was found. Targeting VEGF-A and VEGF-B in macular and retinal vascular diseases, involving neovascularization, may improve treatment outcomes.


Subject(s)
Neovascularization, Pathologic/metabolism , Retinal Diseases/metabolism , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor B/blood , Vitreous Body/metabolism , Aged , Female , Humans , Male , Retrospective Studies
15.
Psychiatry Res Neuroimaging ; 272: 71-78, 2018 02 28.
Article in English | MEDLINE | ID: mdl-29229240

ABSTRACT

Schizophrenia is a severe mental disorder that affects the anatomy and function of the brain, with an impact on one's thoughts, feelings, and behavior. The purpose of the study was to investigate cerebral blood flow (CBF) and brain connectivity in a group of patients with schizophrenia. Pseudo-continuous arterial spin labeling (pCASL) images were acquired from 28 patients in treatment and 28 age-matched healthy controls. Mean CBF and connectivity patterns were assessed. Schizophrenia patients had decreased CBF in the bilateral frontal pole and superior frontal gyrus, right medial frontal gyrus, triangular and opercular parts of the inferior frontal gyrus, posterior division of the left supramarginal gyrus, superior and inferior divisions of the left lateral occipital cortex, and bilateral occipital pole. Moreover, through different methods to assess connectivity, our results showed abnormal connectivity patterns in regions involved in motor, sensorial, and cognitive functions. Using pCASL, a non-invasive technique, we found CBF deficits and altered functional organization of the brain in schizophrenia patients that are associated with the symptoms and characteristics of the disorder.


Subject(s)
Cerebrovascular Circulation/physiology , Magnetic Resonance Imaging/methods , Perfusion Imaging/methods , Schizophrenia/physiopathology , Spin Labels , Adult , Brain/diagnostic imaging , Brain/physiopathology , Brain Mapping , Case-Control Studies , Cognition , Female , Humans , Male , Schizophrenia/diagnostic imaging
16.
Cytokine Growth Factor Rev ; 39: 102-115, 2018 02.
Article in English | MEDLINE | ID: mdl-29248329

ABSTRACT

Vision loss due to disease or degeneration of the eye (retina, choroid, retinal veins, or macula) is a leading cause of blindness worldwide. In most cases, vision-threatening ocular diseases are accompanied by abnormal changes in the vasculature of the eye, especially the retina, and these conditions are collectively referred to as retinal vasculopathies. Impaired blood supply or hypoxia stimulates angiogenesis in the vascular and non-vascular sections of the eye, which results in neovascularization, leading to conditions such as diabetic retinopathy or age-related macular degeneration. Studies show that vascular endothelial growth factors: VEGF-A, VEGF-B, and placental growth factor (PlGF) are elevated in these diseases, and hence, these factors could be used as markers for disease prognosis and therapy. In this review, we discuss the function of these growth factors in normal development and disease, with focus on ocular disorders and emphasize the importance of accurately determining their levels in the vitreous and serum of patients for correct diagnosis and therapy.


Subject(s)
Placenta Growth Factor/metabolism , Retinal Diseases/pathology , Vascular Diseases/pathology , Vascular Endothelial Growth Factors/metabolism , Animals , Biomarkers , Humans , Hypoxia , Mice , Neovascularization, Pathologic/complications , Prognosis , Retinal Diseases/therapy , Vascular Diseases/therapy , Vitreous Body/chemistry
17.
Rev. psiquiatr. clín. (São Paulo) ; 44(6): 149-153, Nov.-Dec. 2017. graf
Article in English | LILACS | ID: biblio-903047

ABSTRACT

Abstract Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investigated whether SNP would have preventative effects on psychogenic symptoms induced by ketamine in healthy subjects. Methods: Healthy subjects (N = 38) were assigned to distinct groups that received SNP in different doses (0.15, 0.25, and 0.5 mcg/kg/min). First, participants received an infusion of SNP or placebo over 75 minutes. After 10 minutes, they were injected for 1 minute with a bolus of 0.26 mg/kg of ketamine and a maintenance dose was started 5 minutes later, with 0.25 mg/kg/h of ketamine for 50 minutes. Results: Ketamine-induced psychopathological alterations induced were reduced by SNP, as assessed with the Brief Psychological Rating Scale. Scores in the objective subscale of the Clinician-Administered Dissociative States Scale were also lower in SNP sessions compared to placebo. SNP had protective effects against deterioration in facial emotion and identity recognition tasks induced by ketamine. Discussion: Our findings support the view that SNP has preventative properties against psychotic manifestations.

19.
Med Sci (Basel) ; 5(3)2017 Aug 09.
Article in English | MEDLINE | ID: mdl-29099033

ABSTRACT

Vascular endothelial growth factor B (VEGF-B) is one of the enigmatic members of the VEGF family. The knowledge gap about VEGF-B expression and how its levels are altered in diabetic eyes were the focus of this investigation that was addressed by comparing and correlating vitreous VEGF-B between diabetic and non-diabetic patients. VEGF-B levels were measured by enzyme-linked immunosorbent assay in vitreous samples (n = 33) from diabetic (n = 25) and non-diabetic (n = 8) patients. Results were compared between groups. Optical coherence tomography from diabetic patients was evaluated for central retinal thickness (CRT) and macular volume (MV). Mean vitreous VEGF-B concentration was higher in diabetic (18.82 ± 1.44 pg/mL ) vs. non-diabetic patients (17.90 ± 0.32 pg/mL) (p = 0.006), and in proliferative diabetic retinopathy (PDR) (19.03 ± 1.52 pg/mL) vs. non-PDR (NPDR) patients (18.18 ±0.96 pg/mL) (p = 0.025). In diabetic retinopathy (DR) patients, correlation between VEGF-B and CRT (µm) was positive and moderate: rs = 0.441 (p ≤ 0.05) and the correlation between VEGF-B and MV (mm³) was positive and robust: rs = 0.716 (p ≤ 0.01). VEGF-B levels are overexpressed in vitreous of diabetic patients, and the levels are higher in developed stages of DR. Correlation results show that CRT and MV increase with increased levels of VEGF-B. Targeting VEGF-B inhibition may have therapeutic beneficial implications.

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