ABSTRACT
Major depressive disorder (MDD) is a debilitating illness that affects millions of people worldwide. Currently available antidepressants often take weeks to months to reach their full effect, which leads to an increased risk of suicidal behavior in patients with MMD. Intranasally, esketamine has emerged as an alternative to current antidepressants because of its rapid onset and long-lasting effects in patients with MDD. Animal models are useful for the initial pharmacological screening and for a better understanding of the mechanisms underlying the effects of new drugs with potential against MDD. There is a lack of data on alternative routes of drug administration, either oral or injectable, that can be used in preclinical studies. This study aimed to test whether ketamine has antidepressant-like effects in mice when administered via nebulization using a low-cost apparatus. When mice whose depressive-like behavior was induced by corticosterone were treated with nebulized ketamine at concentrations of 1.3, 2.6, and 5.2 mg/mL, immobility was reduced by 38.6 %, 62.0 %, and 61.1 %, respectively, in the forced swimming test (FST) and 43.6 %, 42.1 %, and 57.9 %, respectively, in the tail suspension test (TST). When depression-like behavior was induced by dexamethasone, nebulization with ketamine reduced immobility by 79.7 %, 49.2 %, and 44.4 % in the FST and 80.9 %, 71.4 %, and 80.4 %, respectively, in the TST. When depression-like behavior was induced by the association between dexamethasone and unpredictable chronic mild stress (UCMS) exposure, immobility was reduced by 26.1 %, 55.3 %, and 19.1 % in FST. Mice treated with nebulized ketamine did not show significant changes in the distance covered or in the time spent moving in the open field test. The efficacy of intraperitoneal and nebulized ketamine is equivalent, which shows that nebulization can be an alternative inexpensive route of drug administration for behavioral studies in rodents.
Subject(s)
Depressive Disorder, Major , Ketamine , Humans , Mice , Animals , Swimming , Ketamine/pharmacology , Ketamine/therapeutic use , Depressive Disorder, Major/drug therapy , Hindlimb Suspension , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Disease Models, Animal , Dexamethasone/therapeutic use , Depression/drug therapyABSTRACT
SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants, which nears 100% in many settings. New approaches are required to fully exploit serosurvey data. Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titers in serial cross-sectional monthly samples of blood donations across seven Brazilian state capitals (March 2021−November 2021). Using an ecological analysis, we assessed the contributions of prior attack rate and vaccination to antibody titer. We compared anti-S titer across the seven cities during the growth phase of the Delta variant and used this to predict the resulting age-standardized incidence of severe COVID-19 cases. We tested ~780 samples per month, per location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven by vaccination, mean antibody titer increased 16-fold over the study, with the greatest increases occurring in cities with the highest prior attack rates. Mean anti-S IgG was strongly correlated (adjusted R2 = 0.89) with the number of severe cases caused by Delta. Semi-quantitative anti-S antibody titers are informative about prior exposure and vaccination coverage and may also indicate the potential impact of future SARS-CoV-2 variants.
ABSTRACT
Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. Funding: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem.
Subject(s)
COVID-19 , Antibodies, Viral , Blood Donors , Brazil/epidemiology , COVID-19/epidemiology , Cross-Sectional Studies , Female , Humans , Immunoglobulin G , Male , SARS-CoV-2 , Seroepidemiologic StudiesABSTRACT
BACKGROUND: The aim of this study was to retrospectively evaluate the success and survival rate of implants with different types of prosthetic connections inserted in the posterior maxilla in native bone or in sinuses previously grafted with different biomaterials. METHODS: A total of 310 implants inserted in 113 patients were evaluated, 87 of which were inserted in association with grafted maxillary sinuses (56 morse taper (MT) implants and 31 external hexagon (EH) implants) in 37 patients, and 223 implants were inserted in native bone areas (112 MT and 111 EH implants) in 76 patients. Peri-implant clinical analyses were performed (bleeding on probing, probing depth, clinical insertion level, peri-implant marginal level, and the presence of mobility or suppuration), and the radiographic bone level was evaluated. RESULTS: Two implants were lost, yielding a survival rate of 99.35%. The MT implants had lower probing depths and peri-implant bone levels than the EH implants in both grafted areas and native bone areas (P<0.05). No statistically significant differences in any parameter evaluated were found between implants inserted in native bone and those inserted in grafting areas. EH implants inserted in native bone areas showed higher peri-implantitis rates. CONCLUSIONS: It can be concluded that the MT implants connection reduce peri-implant bone loss, but implants inserted in maxillary sinuses previously grafted with osteoconductive biomaterials do not predispose patients to peri-implant bone loss.
Subject(s)
Dental Implants , Maxilla , Dental Implants/adverse effects , Humans , Maxilla/diagnostic imaging , Maxillary Sinus/diagnostic imaging , Retrospective StudiesABSTRACT
Asthma is a chronic inflammatory disease that targeting lower airways, being characterized by bronchial smooth muscle hyper responsiveness and mucus hypersecretion. Asthma is considered the most common respiratory disease in the world, affecting approximately 235 million individuals. The main therapy sometimes fails to establish clinical improvement in patients, which leads to a constant search for new alternatives. Camphor is a transparent solid monoterpene with a strong aroma, which due to its high lipophilicity is insoluble in water. Nanostructured carrier systems have shown promise as a delivery system for lipophilic compounds such as monoterpenes. Therefore, the objective of this work was to evaluate the relaxant effect of nanoemulsified camphor (NEC), as well as the mechanism of action of that monoterpene, in isolated rat trachea. The results obtained demonstrated that NEC promote relaxation of the isolated rat trachea when smooth muscle contraction was induced by both carbachol (CCh) and KCl, presenting a pCE50 of 2.25 ± 0.27 and 3.30 ± 0.07, respectively. In the presence of dexamethasone (DEXA), tetraethylammonium (TEA), glibenclamide (GLIB), 1H-[1,2,4]-oxadiazole-[4,3,-a]-quinoxaline-1-one (ODQ) and ruthenium red (RR) there was a significant difference in at least one of the evaluated pharmacological parameters, such as concentration-response curves shape, Emax or pCE50. As conclusion, NEC may be involved with ß-adrenergic receptors, channels for K+ sensitive to ATP (KATP) or Channels for K+ opened by Ca2+ (KCa), increase in prostanoids and with receptor channel with transient potential (TRPv). In conclusion, ß-adrenergic receptors, prostanoids, nitric oxide (NO), ATP-sensitive K+ channels (KATP), Ca2+-opened K+ channels (KCa), and transient receptor potential cation channel subfamily V (TRPV) are involved in the relaxing effect of NEC. In addition, the mechanism of action of NEC may be involved with the signal transduction pathway Nitric Oxide/soluble guanylyl cyclase/cGMP/cGMP-activated protein kinase. NEC, therefore, demonstrates spasmolytic activity when presenting tracheal relaxation compared to CCh and KCl contracturants.
Subject(s)
Camphor/chemistry , Camphor/pharmacology , Muscle Relaxation/drug effects , Nanostructures/chemistry , Trachea/drug effects , Trachea/physiology , Animals , Emulsions , Male , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Muscle, Smooth/physiology , RatsABSTRACT
INTRODUCTION: Tectocerebellar dysraphia (TCD) is a rare sporadic malformation associated with severe neurodevelopmental morbidity and high infant mortality. The presence of other ciliopathies worsens the prognosis. Joubert syndrome (JS) is a ciliopathy associated with gene mutations, consisting of midbrain and cerebellum malformations, markedly lack fiber decussation at the level of the pontomesencephalic junction. CASE REPORT: We report the case of a child who was born term with occipital encephalocele (OE), diagnosed with TCD and JS spectrum through computed tomography (CT), magnetic resonance (MR), diffuse tensor imaging (DTI), and clinical findings. She had the OE surgically corrected after spontaneous rupture on the second day after delivery. She developed postoperative ventriculitis, meningitis, and hydrocephalus, successfully treated with intravenous antibiotics and cysto-ventriculostomy, cysto-cisternostomy, third ventriculostomy, and choroid plexus coagulation. G-band karyotyping showed 47, XXX, in all analyzed cells (trisomy X). The infant was followed up for 18 months, presenting, so far, a relatively good outcome. CONCLUSION: This is the first case reported in the literature of the association of TCD/OE/JS spectrum (JSS) with trisomy X (XXX).
Subject(s)
Encephalocele , Kidney Diseases, Cystic , Cerebellum/diagnostic imaging , Chromosomes, Human, X , Encephalocele/complications , Encephalocele/diagnostic imaging , Encephalocele/genetics , Female , Humans , Magnetic Resonance Imaging , Sex Chromosome Aberrations , Sex Chromosome Disorders of Sex Development , TrisomyABSTRACT
PURPOSE: To report a unique case of intraocular inflammation and outer retinal changes in a patient with coronavirus disease (COVID-19). CASE REPORT: A 57-year-old woman was seen 12 days after COVID-19 symptoms onset confirmed by positive IgM and IgG serological tests. No anterior chamber cells were seen. Color fundus photograph showed a yellowish lesion within the macular area, and fluorescein angiography revealed hyperfluorescence on the topography of the macular lesion in both eyes. Spectral-domain optical coherence tomography demonstrated hyperreflective pinpoints at the level of posterior vitreous hyaloid, corresponding to vitritis, hyperreflective lesions at the level of inner plexiform and ganglion cell layers, and disruption of the ellipsoid zone. CONCLUSION AND IMPORTANCE: COVID-19 is known to affect the inner retinal layers. The current case not only supports but also adds a vitreal and an outer retinal layer involvement that might also be caused by this infectious disease.
Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Eye Diseases/etiology , Fluorescein Angiography/methods , Pneumonia, Viral/complications , Retinal Photoreceptor Cell Outer Segment/pathology , Tomography, Optical Coherence/methods , Vitreous Body/pathology , COVID-19 , Coronavirus Infections/epidemiology , Eye Diseases/diagnosis , Female , Fundus Oculi , Humans , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Visual AcuitySubject(s)
Cadherins/genetics , Hypotrichosis/genetics , Macular Degeneration/genetics , Stargardt Disease/genetics , Brazil/epidemiology , Exome/genetics , Female , Genetic Predisposition to Disease , Humans , Hypotrichosis/epidemiology , Hypotrichosis/pathology , Macular Degeneration/epidemiology , Macular Degeneration/pathology , Male , Mutation/genetics , Pedigree , Stargardt Disease/epidemiology , Stargardt Disease/pathology , Exome SequencingABSTRACT
The monoterpene alcohol (-)-borneol has many biological effects such as sedative, anti-inflammatory, analgesic, anti-nociceptive, antithrombotic and vasorelaxant effects. Our objective in this study was to investigate the mechanism of action of (-)-borneol and determine its vasorelaxant effect. (-)-Borneol was tested on isolated aortic rings contracted with PE (10-6 m). This study was performed in the absence or in the presence of endothelium, L-NAME (100 µm), indomethacin (10 µm), TEA (1 and 10 mm), 4-AP (1 mm) or glibenclamide (1 mm) to assess the participation of EDRF, nitric oxide, prostanoids and potassium channels on the relaxing effect of (-)-borneol. In this work, (-)-borneol induced a relaxant effect in aortic rings, with and without endothelium, in a concentration-dependent manner. The pharmacological characterization obtained using L-NAME, indomethacin, TEA, 4-AP and glibenclamide demonstrates that the effect of (-)-borneol was modified in the presence of L-NAME, indomethacin and glibenclamide showing that these signal transduction pathways are involved in the relaxing effect of the monoterpene. (-)-Borneol has a vasorelaxant effect that depends on the presence of vascular endothelium, with the participation of nitric oxide and prostanoids. Also, (-)-borneol displayed a direct action on the vascular smooth muscle, greatly dependent on KATP channels.
Subject(s)
Aorta/drug effects , Camphanes/pharmacology , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Animals , Aorta/metabolism , Dose-Response Relationship, Drug , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , In Vitro Techniques , KATP Channels/metabolism , Male , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Nitric Oxide/metabolism , Prostaglandins/metabolism , Rats, Wistar , Signal Transduction/drug effectsABSTRACT
In this work, two methods were developed to determine herbicides paraquat, glyphosate, and aminomethylphosphonic acid (AMPA) in marijuana samples by capillary electrophoresis. For paraquat analysis, sample was extracted with aqueous acetic acid solution and analyzed by capillary zone electrophoresis with direct UV detection. The running electrolyte was 50 mmol/L phosphate buffer (pH 2.50). For glyphosate and AMPA, indirect UV/VIS detection was used, as these substances do not present chromophoric groups. Samples were extracted with 5 mmol/L hydrochloric acid. The running electrolyte was 10 mmol/L gallic acid, 6 mmol/L TRIS, and 0.1 mmol/L CTAB (pH = 4.7). The methods presented good linearity, precision, accuracy, and recovery. Paraquat was detected in 12 samples (n = 130), ranging from 0.01 to 25.1 mg/g. Three samples were positive for glyphosate (0.15-0.75 mg/g), and one sample presented AMPA as well. Experimental studies are suggested to evaluate the risks of these concentrations to marijuana user.
Subject(s)
Cannabis/chemistry , Glycine/analogs & derivatives , Herbicides/analysis , Organophosphonates/analysis , Paraquat/analysis , Drug Contamination , Electrophoresis, Capillary , Glycine/analysis , Isoxazoles , Tetrazoles , GlyphosateABSTRACT
Os autores analisam 50 casos de luxação acromioclavicular aguda tratados cirurgicamente por redução cruenta e fixação com amarilho coracoclavicular com fio inabsorvível de grosso calibre. Para isso, reúnem a experiência de quatro serviços de cirurgia do ombro que utilizaram a mesma técnica operatória e avaliam a eficiência do método de fixação. Verificam que em 40 pacientes (80 por cento) a redução conseguida se manteve e a distância coracoclavicular não se alterou. Em 6 pacientes (12 por cento) ocorreu migração superior da clavícula quando comparada com a redução conseguida no pós-operatório imediato. Em 4 pacientes (8 por cento) houve falência da fixação e perda completa da redução. Observam que o método de fixação com reparo coracoclavicular utilizando fios inabsorvíveis de grosso calibre mostrou resultados satisfatórios no que diz respeito à manutenção da redução obtida durante o ato cirúrgico.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Acromioclavicular Joint/injuries , Fracture Fixation, Internal/methods , Joint Dislocations/surgery , Clavicle/surgeryABSTRACT
A investigaçäo em tela analisa os resultados referentes ao perfil da hemoglobina umbilical do recém-nascido, comparativamente ao último exame cardiotocográfico anteparto, basal e de esforço (estímulo do mamilo e/ou teste de ocitocina). Foram acompanhados 41 conceptos, número idêntico de gestantes, todas previamente sensibilizadas pelo fator Rh. O traçado reativo negativo, em 27 casos, foi compatível em 20 com valor de hemoglobina superior à 12g//. Caso único evidenciou 11,6g//. Em contrapartida, no grupo reativo positivo (seis casos) apenas um exibiu taxa de 12,4g. Os restantes (quatro casos) mostraram variaçäo entre 5g// e 10,8g//. O traçado näo-reativo positivo (oito casos) correspondeu a valores da hemoglobina inferiores a 10g// (variaçäo entre 2,8g// e 9,3g//). Neste grupo inscrevem-se três conceptos com morte neonatal imediata. A oscilaçäo sinusóide foi detectada uma só vez. Do exposto, afigura-se o propósito da cardiotocografia em circunstanciar o risco fetal relativo à avaliaçäo gráfica de Liley
Subject(s)
Humans , Female , Pregnancy , Infant, Newborn , Cardiotocography , Maternal-Child Nursing , Fetal Blood , Hemoglobins , Pregnancy, Animal , Umbilical CordABSTRACT
Procurou-se mostrar a importância da estimulaçäo precoce para o deficiente visual näo só no que concerne a parte visual mas analisando-se também a parte física e intelectual do deficiente. Relata-se a equipe necessária para a formaçäo de um departamento de estimulaçäo precoce e a reaçäo dos pais diante de un filho deficiente