Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs

BACKGROUND Distinct N-acetyltransferase 2 (NAT2) slow acetylators genotypes have been associated with a higher risk to develop anti-tuberculosis drug-induced hepatotoxicity (DIH). However, studies have not pointed the relevance of different acetylation phenotypes presented by homozygotes and compound heterozygotes slow acetylators on a clinical basis. OBJECTIVES This study aimed to investigate the association between NAT2 genotypes and the risk of developing DIH in Brazilian patients undergoing tuberculosis treatment, focusing on the discrimination of homozygotes and compound heterozygotes slow acetylators. METHODS/FINDINGS The frequency of NAT2 genotypes was analysed by DNA sequencing in 162 patients undergoing tuberculosis therapy. The mutation analyses revealed 15 variants, plus two new NAT2 mutations, that computational simulations predicted to cause structural perturbations in the protein. The multivariate statistical analysis revealed that carriers of NAT2*5/*5 slow acetylator genotype presented a higher risk of developing anti-tuberculosis DIH, on a clinical basis, when compared to the compound heterozygotes presenting NAT2*5 and any other slow acetylator haplotype [aOR 4.97, 95% confidence interval (CI) 1.47-16.82, p = 0.01]. CONCLUSION These findings suggest that patients with TB diagnosis who present the NAT2*5B/*5B genotype should be properly identified and more carefully monitored until treatment outcome in order to prevent the occurrence of anti-tuberculosis DIH.

A Molécula de Lesão Renal-1 está Associada à Nefropatia Induzida por Contraste em Pacientes Idosos com IAMSSST / Kidney Injury Molecule-1 Is Associated with Contrast-Induced Nephropathy in Elderly Patients with Non-STEMI

Resumo Fundamento A nefropatia induzida por contraste (NIC) está associada a um risco aumentado de eventos cardiovasculares adversos maiores (ECAM), e a associação entre NIC e mecanismos oxidativos está bem documentada. Objetivo Este estudo visou avaliar a relação entre os níveis séricos da molécula de lesão renal-1 (KIM-1) e a NIC em pacientes idosos com infarto do miocárdio sem supradesnivelamento do segmento ST (IAMSSST). Métodos O presente estudo incluiu um total de 758 pacientes com IAMSSST que foram submetidos a intervenção coronária percutânea (ICP); 15 desenvolveram NIC após a ICP e outros 104 constituíram o grupo controle, pareado por idade > 65 anos. Foram registrados os valores laboratoriais desde a linha de base até o período entre 48 e 72 horas e os achados clínicos. Os pacientes foram acompanhados durante um ano. Foram considerados significativos valores de p < 0,05. Resultados A NIC foi observada em 12,60% dos pacientes. A KIM-1 sérica foi significativamente mais alta no grupo com NIC que no grupo sem NIC (14,02 [9,53 - 19,90] versus 5,41 [3,41 - 9,03], p < 0,001). O escore Mehran foi significativamente mais alto no grupo com NIC do que no grupo sem NIC (14 [5 - 22] versus 5 [2 - 7], p = 0,001). Os ECAM foram significativamente maiores no grupo com NIC do que no grupo sem NIC (7 [46,70%] versus 12 [11,50%], p = 0,001). A análise de regressão logística multivariada mostrou que o nível de KIM-1 basal (OR = 1,652, IC 95%: 1,20 - 2,27, p = 0,002) e o escore Mehran (OR = 1,457, IC 95%: 1,01 - 2,08, p = 0,039) foram preditores independentes da NIC em pacientes idosos com IAMSSST. Conclusão A concentração sérica basal de KIM-1 e o escore de Mehran são preditores independentes de NIC em pacientes idosos com IAMSSST. Além disso, todas as causas de mortalidade, morte cardiovascular, reinfarto do miocárdio, acidente vascular cerebral e MACE foram significativamente maiores no grupo CIN no acompanhamento de um ano. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Abstract Background Contrast-induced nephropathy (CIN) is associated with an increased risk of major adverse cardiovascular events (MACE), and the association between CIN and oxidative mechanisms is well documented. Objective This study aimed to evaluate the relationship between serum levels of kidney injury molecule-1 (KIM-1) and CIN in elderly patients with non-ST-segment elevation myocardial infarction (NSTEMI). Methods This study included a total of 758 patients with NSTEMI, who underwent percutaneous coronary intervention (PCI); 15 developed CIN after PCI, and another 104 were the control group, matched for age > 65 years. Baseline to 48-to-72-hour laboratory values and clinical outcomes were recorded. Patients were followed during one year. P values of < 0.05 were considered significant. Results CIN was observed in 12.60% of the patients. Serum KIM-1 was significantly higher in the CIN group than in the non-CIN group (14.02 [9.53 - 19.90] vs. 5.41 [3.41 - 9.03], p < 0.001). The Mehran score was significantly higher in the CIN group than in the non-CIN group (14 [5 - 22] vs. 5 [2 - 7], p = 0.001). MACE were significantly higher in the CIN group than in the non-CIN group (7 [46.70%] vs. 12 [11.50%], p = 0.001). Multivariate logistic regression analysis showed that baseline KIM-1 level (OR = 1.652, 95% CI: 1.20 - 2.27, p = 0.002) and Mehran score (OR = 1.457, 95% CI: 1.01 - 2.08, p = 0.039) were independent predictors of CIN in elderly patients with NSTEMI. Conclusion Baseline serum KIM-1 concentration and Mehran score are independent predictors of CIN in elderly patients with NSTEMI. Additionally, all-cause mortality, cardiovascular death, myocardial reinfarction, stroke, and MACE were significantly higher in the CIN group at one-year follow-up. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Acute angle closure triggered by oral benzodiazepines / Fechamento angular agudo desencadeado por uso oral de benzodiazepínicos

ABSTRACT Benzodiazepines are psychoactive drugs that are prescribed worldwide with limited information on their ocular side effects. Acute angle closure glaucoma is an adverse event with a high risk of blinding, especially in the elderly. We report two patients under 45 years old who presented with bilateral acute angle closure secondary to use of two long half-life benzodiazepines (clonazepam and alprazolam). In addition to suspending the use of these medications and administering ocular hypotensive drugs, both patients were successfully treated with bilateral peripheral laser iridotomy. To the best of our knowledge, this is the first report of bilateral acute angle closure secondary to the use of clonazepam and alprazolam.(AU)

RESUMO Os benzodiazepínicos são medicamentos psicoativos prescritos em todo o mundo, mas com poucas informações sobre seus efeitos colaterais oculares. O glaucoma por fechamento agudo do ângulo iridocorneano é um dos eventos adversos com maior risco de cegueira, sendo descrito particularmente em idosos. Relatamos aqui dois pacientes com menos de 45 anos de idade, com fechamento agudo do ângulo bilateral secundário ao uso de dois diferentes benzodiazepínicos de meia-vida longa (clonazepam e alprazolam). Além da suspensão dessas medicações e do tratamento clínico com drogas hipotensoras oculares, ambos os casos alcançaram sucesso com iridotomias periféricas bilaterais à laser. Considerando o conhecimento atual, estes são os primeiros relatos de fechamento agudo do ângulo bilateral secundária ao uso de clonazepam e alprazolam.(AU)

Encefalopatia reversível induzida por contraste após embolização com espiras por epistaxe / Reversible contrast-induced encephalopathy after coil embolization of epistaxis

RESUMO Uma mulher com 37 anos de idade, gestante de 35 semanas, foi admitida em um hospital local em razão de epistaxe grave, que resultou em choque e em necessidade de realização de cesárea emergencial. Após falha do tamponamento para controlar a hemorragia, decidiu-se por tratamento angiográfico. Após o procedimento, ela foi admitida à unidade de terapia intensiva neurocrítica, encontrando-se confusa e agitada, com necessidade de sedação e intubação orotraqueal. Na unidade de terapia intensiva, as investigações incluíram exames de ressonância magnética, punção lombar com painel viral, eletroencefalograma, testes para autoimunidade e avaliações hidroeletrolítica e metabólica. O exame de ressonância magnética mostrou área puntiforme restrita na corona radiata esquerda nas sequências de imagens pesadas em difusão, além de leve edema cortical posterior (sem restrição à difusão), e o eletroencefalograma mostrou atividade lenta difusa moderada, atividade frontoparietal lenta e escassos componentes paroxísticos associados no hemisfério esquerdo. Outros exames não mostraram alterações relevantes. Por causa da relação temporal e da história clínica, assim como imagens de ressonância magnética, formulou-se o diagnóstico de encefalopatia induzida por contraste. A sedação foi retirada após 2 dias na unidade de terapia intensiva, e a paciente foi extubada, verificando-se completa recuperação neurológica dentro das 24 horas seguintes.

ABSTRACT A 37-year-old woman (35 weeks pregnant) was admitted to a local hospital due to severe epistaxis resulting in shock and the need for emergency cesarean section. After failure to tamponade the bleeding, angiographic treatment was provided. After the procedure, she was admitted to the neurocritical intensive care unit and was confused and agitated, requiring sedation and endotracheal intubation. In the intensive care unit, diagnostic investigations included brain magnetic resonance imaging, lumbar puncture with viral panel, electroencephalogram, tests for autoimmunity, and hydroelectrolytic and metabolic evaluations. Magnetic resonance imaging showed a puntiform restricted diffusion area on the left corona radiata on diffusion weighted imaging and mild cortical posterior edema (without restricted diffusion), and an electroencephalogram showed moderate diffuse slow activity and fronto-temporal slow activity of the left hemisphere with associated scarce paroxysmal components. The other exams did not show any relevant alterations. Due to the temporal relationship, the clinical history and the magnetic resonance imaging results, a diagnosis of contrast-induced encephalopathy was made. After 2 days in the intensive care unit, sedation was withdrawn, the patient was extubated, and total neurological recovery was verified within the next 24 hours.

Spontaneous repositioning of posterior chamber intraocular lens: a mere coincidence? / Reposicionamento espontâneo de uma lente intraocular na câmara posterior: uma mera coincidência?

ABSTRACT Despite the recent developments in modern cataract surgery and the application of a vast array of new devices and machines, late in-the-bag intraocular lens dislocation remains a devastating, albeit rare, complication. Various nonsurgical and surgical techniques have been used to manage this complication. We report a case of spontaneous repositioning in the left eye of an anteriorly subluxated in-the-bag intraocular lens. The spontaneous repositioning may have been caused by antagonistic effects related to the topical administration of brimonidine and prednisolone. The dislocation was treated without aggressive manipulation or surgical intervention.

RESUMO Apesar dos recentes avanços na cirurgia moderna de catarata e da aplicação de uma ampla gama de novos dispositivos, o deslocamento tardio de uma lente intraocular dentro do saco capsular continua a ser uma complicação devastadora, ainda que rara. Várias técnicas cirúrgicas e não cirúrgicas têm sido usadas para tratar esta complicação. Este é o relato de um caso de reposicionamento espontâneo de uma lente intraocular sub-luxada anteriormente dentro do saco capsular do olho esquerdo. Este reposicionamento pode ter sido causado pelos efeitos opostos da aplicação tópica simultânea de brimonidina e prednisolona. O deslocamento foi tratado sem manipulação agressiva ou intervenção cirúrgica.

Diseases, conditions, and drugs associated with cicatricial ectropion / Doenças, condições e drogas associadas ao ectrópio cicatricial

ABSTRACT Cicatricial ectropion may be a consequence of certain systemic diseases as well as the result of drug use. Our goal here was to research the different causes of this condition as reported in the literature, including more recently suspected etiologies. A detailed PubMed literature search indicated many different etiologies were associated with cicatricial ectropion development, from severe cases of systemic diseases, such as ichthyosis and lupus erythematosus, to reversible scenarios secondary to anti-glaucomatous drug use. More recently reported connections include periorbital necrotizing fasciitis, frontal osteomyelitis, and antineoplastic agents. Indeed, cicatricial ectropion may be highly symptomatic; being able to determine its real etiology is imperative to managing patients properly. In this investigation, we felt that an explicitly multidisciplinary approach was essential, especially for cases associated with systemic conditions.

RESUMO O ectrópio cicatricial pode ser uma consequência de certas doenças sistêmicas, bem como o resultado do uso de drogas. Nosso objetivo aqui foi pesquisar as diferentes causas desta condição, conforme relatado na literatura, incluindo mais recentemente suspeitas de etiologias. Uma pesquisa bibliográfica detalhada do PubMed indicou que muitas etiologias diferentes estavam associadas ao desenvolvimento do ectrópio cicatricial, desde casos graves de doenças sistêmicas, como ictiose e lúpus eritematoso, até cenários reversíveis secundários ao uso de drogas antiglaucomatosas. Conexões relatadas mais recentemente incluem fasceíte necrosante periorbitária, osteomielite frontal e agentes antineoplásicos. De fato, o ectrópio cicatricial pode ser altamente sintomático; ser capaz de determinar sua etiologia real é imperativo para o manejo adequado dos pacientes. Nesta investigação, sentimos que uma abordagem explicitamente multidisciplinar era essencial, especialmente para casos associados a doenças sistêmicas.

Agrandamiento gingival medicamentoso en paciente con trasplante renal tratado con ciclosporina A / Drug-induced gingival enlargement in a kidney transplant patient treated with cyclosporine A

Resumen El agrandamiento gingival medicamentoso se describe como un aumento de volumen anormal, exagerado y deformante de las encías, provocado por la ingesta de algunos medicamentos. Entre los más comunes se encuentran: fármacos anticonvulsivantes, antihipertensivos, particularmente los antagonistas del calcio e inmunosupresores. Se presentó el caso de un paciente del sexo masculino, de 44 años de edad, con antecedentes de hipertensión arterial e insuficiencia renal crónica, durante 10 y tres años respectivamente. Después de 22 meses de haber recibido un trasplante renal y tratamiento con ciclosporina, acude a consulta por aumento del volumen de las encías en ambos maxilares, clínicamente compatible con agrandamiento gingival medicamentoso generalizado y grave.

ABSTRACT Drug-induced gingival enlargement is described as an abnormal, exaggerated, and deforming growth of the gingiva caused by the ingestion of some medications. Anticonvulsants, antihypertensive calcium channel blockers and immunosuppressants are among the most common drugs. We present a 44-year-old male patient with a history of arterial hypertension and chronic renal failure, for 10 and three years, respectively. Twenty-two months after receiving a kidney transplant and treatment with cyclosporine, he visited the clinic due to an increase in the volume of the gums in both jaws, clinically compatible with a generalized and severe gingival enlargement.

Delay of neuropathic pain sensitization after application of dexamethasone-loaded implant in sciatic nerve-injured rats

Neuroimmune interactions underlying the development of pain sensitization in models of neuropathic pain have been widely studied. In this study, we evaluated the development of allodynia and its reduction associated with peripheral antineuroinflammatory effects induced by a dexamethasone-loaded biodegradable implant. Chronic constriction injury (CCI) of the sciatic nerve was performed in Wistar rats. The electronic von Frey test was applied to assess mechanical allodynia. The dexamethasone-loaded implant was placed perineurally at the moment of CCI or 12 days after surgery. Dorsal root ganglia (DRG; L4-L5) were harvested and nuclear extracts were assayed by Western blot for detection of nuclear factor (NF)-κB p65/RelA translocation. Dexamethasone delivered from the implant delayed the development of allodynia for approximately three weeks in CCI rats when the implantation was performed at day 0, but allodynia was not reversed when the implantation was performed at day 12. NF-κB was activated in CCI rat DRG compared with naïve or sham animals (day 15), and dexamethasone implant inhibited p65/RelA translocation in CCI rats compared with control. This study demonstrated that the dexamethasone-loaded implant suppresses allodynia development and peripheral neuroinflammation. This device can reduce the potential side effects associated with oral anti-inflammatory drugs.

Síndrome pseudo Bartter asociado a la infusión endovenosa de colistina

RESUMEN El Síndrome Pseudo Bartter (PB) es una patología rara que consiste en una tubulopatía perdedora de sal debida a una alteración en la función de la rama ascendente del asa de Henle. Puede estar asociada con el uso de fármacos como la colistina. Conduce a una disminución sérica de electrolitos en sangre con hiperreninemia, hiperaldosteronemia y alcalosis metabólica, con repercusión en el área neuromotora y cardiovascular principalmente. Presentamos una serie de 3 pacientes que recibieron tratamiento con colistina, con edad media 66,6±20,4 años, predomino del sexo femenino. El Síndrome PB apareció a los 13,6±4,7 días del uso de colistina. Tras la instauración terapéutica presentaron disminución sérica de calcio, potasio y magnesio, acompañados de alcalosis metabólica y normotensión, resolviendo el cuadro a los 5,6±3,2 días. La aparición del Síndrome PB tras el uso de la colistina es rara, las alteraciones producidas por la tubulopatía no responden a la corrección insistente de los déficits solamente, requieren de tratamiento adicional para su resolución. La falta de conocimiento de esta complicación puede presentar desenlaces fatales para los pacientes y una intervención oportuna produce soluciones aparentemente alentadoras.

ABSTRACT Pseudo Bartter Syndrome (PB) is a rare pathology that consists of a salt-losing tubulopathy due to an alteration in the function of the ascending limp of the loop of Henle. It may be associated with the use of drugs such as colistin. It leads to a serum decrease of blood electrolytes with hyperreninism, hyperaldosteronism and metabolic alkalosis, with repercussion in the neuromotor and cardiovascular areas mainly. We present a series of 3 patients who received treatment with colistin, with a mean age of 66,6±20,4 years, predominantly female. PB Syndrome appeared at 13,6±4,7 days after the use of colistin. After the therapeutic initiation they presented serum decrease of calcium, potassium and magnesium, accompanied by metabolic alkalosis and normal blood pressure, all of them have shown resolution of the metabolic disturbances at 5,6±3,2 days. The appearance of PB Syndrome after the use of colistin is rare. The alterations produced by the tubulopathy do not respond to the insistent correction of the deficits only and require additional treatment for their resolution. The lack of knowledge of this complication could lead to fatal outcomes for patients and a timely intervention produces apparently encouraging solutions.

Neuropatia óptica tóxica por inalação de metanol / Optic neuropathy toxic after methanol inhalation

Resumo A intoxicação por metanol é um evento considerado raro, principalmente quando feita por via inalatória. Retratou-se neste presente estudo um relato de caso de um paciente que desenvolveu neurite óptica tóxica após exposição ao metanol e ácido acético por via inalatória em seu ambiente de trabalho. Foi descrito sobre as terapias obtidas na literatura, bem como as manifestações clínicas e o manejo a este paciente.

Abstract The methanol toxicity is considered rare event , especially when taken by inhalation . It was portrayed in the present study a case report of a patient who developed toxic optic neuritis after exposure to methanol and acetic acid by inhalation in the workplace . It was described for the therapies from the literature as well as the clinical manifestations and management in this patient.

Chemotherapy protocols and incidence of oral mucositis. An integrative review / Protocolos quimioterápicos e incidência de mucosite bucal. Revisão integrativa

ABSTRACT This review aimed to analyze the scientific production on severity of oral mucositis as an adverse effect of chemotherapy. To this end, we performed a search at PubMed databases combining the keywords "oral mucositis" and "chemotherapy protocol". To describe the investigation, the following variables were considered: journal, year/place, study design, sample, protocol used and incidence of oral mucositis. A total of 547 articles were retrieved, of which 26 were selected. Out of these 26, only 2 reported severity of oral mucositis; the others only reported the presence of the condition. Protocols for treating different types of carcinoma were evaluated in 16 (61.53%) studies, for hematological malignancies in 6 (23.07%), and for hematopoietic stem cell transplantation in 4 (15.4%). Protocols for hematopoietic stem cell transplantation entail a high risk for oral mucositis, just as chemotherapy with cytarabine and high-dose 5-fluorouracil, alkylating agents and platinumbased compounds. To provide the best prevention and treatment for oral mucositis, it is essential to know the chemotherapy protocols used and their effects on the oral cavity.

RESUMO Esta revisão teve como objetivo analisar a produção científica sobre a gravidade da mucosite oral como efeito adverso da quimioterapia. Para tal, nos bancos de dados do PubMed, foi realizada uma busca com a associação dos descritores "oral mucositis" com "chemotherapy protocol". Para descrição da investigação, foram consideradas como variáveis: periódico, ano/local, delineamento da pesquisa, amostra, protocolo utilizado e incidência de mucosite oral. Foram analisados 547 artigos e, destes, 26 foram selecionados. Destes 26, apenas 2 tinham como objetivo avaliar a gravidade de mucosite oral; nos outros, a mucosite oral foi apenas relatada. Protocolos para tratamento de diferentes tipos de carcinoma foram avaliados em 16 (61,53%) estudos, para neoplasias hematológicas, em 6 (23,07%), e para transplante de células tronco hematopoiéticas em 4 (15,4%). Protocolos para transplante de células tronco hematopoiéticas são de alto risco para o desenvolvimento de mucosite oral, da mesma forma que os quimioterápicos citarabina e 5-fluorouracil em altas doses, agentes alquilantes e compostos derivados da platina. A fim de oferecer prevenção e tratamento mais adequados para mucosite oral, é imprescindível que se conheçam os protocolos quimioterápicos utilizados e seus efeitos sobre a cavidade oral.

Lesão renal aguda induzida por contraste: importância dos critérios diagnósticos para estabelecer a prevalência e o prognóstico na unidade de terapia intensiva / Contrast-induced acute kidney injury: the importance of diagnostic criteria for establishing prevalence and prognosis in the intensive care unit

RESUMO Objetivo: Estabelecer se há superioridade entre os critérios para predizer desfecho clínico desfavorável na lesão renal aguda e nefropatia induzidas por contraste. Métodos: Estudo retrospectivo conduzido em hospital terciário com 157 pacientes submetidos à infusão de contraste radiológico para fins propedêuticos. Resultados: Cumpriram os critérios para inclusão 147 pacientes. Aqueles que cumpriram os critérios de lesão renal aguda induzida por contraste (59) também cumpriram os critérios para nefropatia induzida por contraste (76); 44,3% dos pacientes cumpriram os critérios para o estadiamento pelo sistema KDIGO; 6,4% dos pacientes necessitaram utilizar terapia de substituição renal, e 10,7% dos pacientes morreram. Conclusão: O diagnóstico de nefropatia induzida por contraste foi o critério mais sensível para determinar a necessidade de terapia de substituição renal e óbito, enquanto o KDIGO demonstrou a maior especificidade; na população avaliada, não houve correlação entre o volume de contraste e a progressão para lesão renal induzida por contraste, nefropatia induzida por contraste, diálise de suporte ou óbito.

ABSTRACT Objective: To establish whether there is superiority between contrast-induced acute kidney injury and contrast-induced nephropathy criteria as predictors of unfavorable clinical outcomes. Methods: Retrospective study carried out in a tertiary hospital with 157 patients undergoing radiocontrast infusion for propaedeutic purposes. Results: One hundred forty patients fulfilled the inclusion criteria: patients who met the criteria for contrast-induced acute kidney injury (59) also met the criteria for contrast-induced nephropathy (76), 44.3% met the criteria for KDIGO staging, 6.4% of the patients required renal replacement therapy, and 10.7% died. Conclusion: The diagnosis of contrast-induced nephropathy was the most sensitive criterion for renal replacement therapy and death, whereas KDIGO showed the highest specificity; there was no correlation between contrast volume and progression to contrast-induced acute kidney injury, contrast-induced nephropathy, support dialysis or death in the assessed population.

Protective effects of citric acid-disodium hydrogen phosphate rinsing solution on ocular surface of mice with acute chemically induced corneal burns / 中华实验眼科杂志

Background Immediately ocular rinsing is a key step for the prevention of eye tissue damage after acute chemical bums.A good ophthalmic rinsing solution can neutralize chemical substance and improve the prognosis of patients.Objective This study attempted to evaluate the therapeutic effect of self-made citric aciddisodium hydrogen phosphate buffer and citric acid-disodium hydrogen phosphate-potassium chloride buffer on corneal chemical burns in mice.Methods Citric acid-disodium hydrogen phosphate buffer solution (solution 1) and citric acid-disodium hydrogen phosphate-potassium chloride buffer solution (solution2) with the pH 7.4 were prepared.One hundred and twenty clean male C57 mice aged 6-8 weeks were randomized to two groups,and filter papers containing 1 mol/L H2SO4 or 0.15 mol/L NaOH were attached to the central corneas of the right eyes to create the acid or alkali burning models.Then the eyes were immediately rinsed by 40 ml solution 1,tap water or solution 2 according to the grouping and the model eyes without rinsing served as the control group.The corneal opacity was examined by slit lamp microscope and scored in 3,7 and 14 days after modeling.The percentages of corneal fluorescein staining,corneal neovascularization and corneal ulcer were analyzed.The study protocol was approved by Experimental Animal Ethic Commission of Second Military Medical University.Results In the corneal acid burning models,the number of eye with corneal opacity scored 1 in the solution 1 group,tap water group and solution 2 group was significantly more than that in the non-rinsing group in 3,7 and 14 days after modeling (all at P＜0.01);In 3 days after modeling,the numbers of eye scored 1 were more in the solution 1 group than those in the tap water group and solution 2 group (x2 =11.000,P =0.001;x2 =4.000,P =0.046).There were no differences in the eye number of different corneal opacity scores in 14 days after acid burning (all at P＞0.05).In 3,7 and 14 days after corneal alkali burning,the number of eyes with corneal opacity scored 1-2 was significantly increased in the solution 1 group,tap water group and solution 2 group compared with non-rinsing group (all at P＜0.01).The percentage of corneal ulcer in the solution 1 group,tap water group and solution 2 group was 7％,27％ and 13％,respectively,which was significantly lower than 73％ in the non-rinsing group (P =0.000,0.027,0.003),and no significant differences were seen in various time points after corneal alkali burning (all at P＞O.05).Corneal neovascularization occurred in 50％ mice in non-rinsing group in 14 days after acid burning.However,no neovascularization was seen in the mice of the solution 1 group,tap water group and solution 2 group in both acid and alkali burning mice.Conclusions Citric aciddisodium hydrogen phosphate buffer (pH 7.4) appears to be an effective emergency rinsing solution for corneal chemical burns and the rinsing solution with or without potassium chloride is not obviously affected to the prognosis of corneal chemical burns in the mice.

Promoting ocular surface restoration effects and anti-inflammatory mechanism of thymosin beta 4 in rat dry eye / 中华实验眼科杂志

Background Studies showed that inflammation is associated with the pathogenesis and development of dry eyes,and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) are key inflammatory factors.Thymosin β4 (Tβ4) plays a promoting effect on the migration of epithelial cells and anti-inflammatory action.However,the influences of Tβ4 on the repair of ocular surface in dry eyes are unelucidated.Objective This study was to investigate the regulation of Tβ4 to the expressions of TNF-o and IFN-γand its effect on the recovery of ocular surface in rat dry eye models.Methods The dry eye models were induced by topically administered of benzalkonium chloride (BAC) for consecutive 7 days in the left eyes of 50 SPF male SD rats,and 36 successful models were used in the experiment.Tβ4 solution (9 μg/ml),recombinant human epithelial growth factor (rhEGF)and sterile PBS at 5 μl was topically administered three times for consecutive 7 days in the Tβ4 group,rhEGF group and PBS group,and no drug was used in the model control group.The normal right eyes of rats served as the normal control group.The break-up time of tear film (BUT),corneal fluorescein staining score and Schirmer Ⅰ test (S I t)were examined and evaluated in the rats on the seventh day after administration of drugs.Then the rats were sacrificed by excessive anesthesia and the sections of the ocular surface were prepared.The morphology of the specimens was examined by hematoxylin and eosin staining,and the number of conjunctival gobelt cells was counted by periodic acidschiff staining.The ultrastructure of the corneal and conjunctival cells was examined under the transmission electron microscope.The expressions of TNF-α mRNA and IFN-γ mRNA and their proteins in conjunctiva tissue were quantified by quantitative real-time PCR and Western blot,respectively.The use and care of the animals followed by Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The BUT was (10.42±0.66),(7.46±0.49),(8.71±0.50),(9.59±0.35) and (8.63± 0.68) seconds in the normal control group,model control group,rhEGF group,Tβ4 group and BUT group,showing a significant difference among the groups (F =5.65,P =0.00),and the BUT was evidently shortened in the model control group compared with the normal control group,while the BUT was significantly extended in the rhEGF group and Tβ4 group in comparison with the model control group (all at P＜0.05).No significant differences were found in the corneal fluorescence score and S I t among the groups (F =0.42,P =0.79;F =136.77,P =0.00).The corneal and conjunctival epithelium defect and corneal stromal edema were seen in the model control group,and the proliferation of the epithelial cells were found in the rhEGF group and Tβ4 group,with the irregulated arrangement of the cells.A considerable difference was seen in the number of conjunetival goblet cells among the groups (F=3.16,P =0.04),and the number of eonjunctival goblet cells in the rhEGF group and model control group was significantly less than that in the normal control group (all at P＜0.05),and no statistically significant difference was seen between Tβ4 group and normal control group (P ＞ 0.05).The swelling,mergence,crispation,rupture and decrease of the microvilli and micro fold were found in the model control group,and the repair of the cell microvilli was seen in the Tβ4 group.The expressions of the TNF-α mRNA,IFN-γ mRNA and their proteins in the conjunctiva were significantly different among the groups (F =43.08,371.69,34.27,43.52,all at P =0.00),the expressions of the inflammatory factors were significantly higher in the model control group compared with the normal control group,and these expressions were evidently lower in the Tβ4 group in comparison with the model control group and rhEGF group (all at P＜0.05).Conclusions The topical administration of Tβ4 solution can promote the repair of ocular surface by down-regulating the expression of TNF-α and IFN-γ in conjunctiva and stablize the tear film in rat dry eyes.

Anti-inflammatory effect of lycopene on endotoxin-induced uveitis in rats / Efeito anti-inflamatório do licopeno na uveíte induzida por endotoxina em ratos

ABSTRACT Purpose: We evaluated the efficacy of lycopene, a dietary carotenoid and potent antioxidant, against ocular inflammation and oxidative stress in an experimental uveitis model. Methods: Endotoxin-induced uveitis (EIU) was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 μg lipopolysaccharide (LPS). Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group) or equivolume vehicle (Vehicle + LPS group). A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS), and a negative control group received daily vehicle injection but no LPS (Vehicle Control). Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically. Results: Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 μM vs. 0.19 ± 0.1 μM, p=0.003), TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043), and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008). Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001). Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone. Conclusions: Lycopene may aid in the clinical management of uveitis by suppressing inflammation and oxidative stress.

RESUMO Objetivo: Avaliamos o efeito do licopeno, um carotenóide dietético e um potente anti-oxidante, sobre a inflamação ocular e estresse oxidativo em modelo de uveíte experimental. Métodos: Uveíte foi induzida por endotoxina (EIU) em ratos Sprague-Dawley por uma única injeção subcutânea de 200 ug de lipopolissacárido (LPS). A indução de EIU foi precedida por injeção intraperitoneal de licopeno em uma dose de 10 mg/kg (grupo LPS + Licopeno) ou veículo de mesmo volume (grupo LPS + Veículo), durante 3 dias consecutivos. O grupo controle positivo recebeu uma dose de 1 mg/kg de Dexametasona (grupo DEX + LPS) e o grupo controle negativo recebeu doses diárias de veículo mas sem LPS (grupo Controle Veículo). Vinte e quatro horas após a administração do LPS, os olhos foram enucleados, humor aquoso foi recolhido, e o número de células infiltrativas, a concentração de proteína, assim como os níveis de óxido nítrico (NO), fator de necrose tumoral α (TNF-α), interleucina-6 e marcadores de estresse oxidativo foram determinados no humor aquoso. Além disso, a resposta inflamatória foi avaliada clinicamente e histologicamente. Resultados: As células infiltrativas, concentração de proteína, o NO, TNF-α, interleucina-6 foram significativamente elevados no humor aquoso de ratos do grupo Grupo LPS + Veículo quando comparados ao Grupo Controle Veículo. O tratamento com licopeno diminuiu significativamente estes aumentos. Comparado ao Grupo LPS + Veículo, o licopeno reduziu significativamente as concentrações no humor aquoso dos marcadores de estresse oxidativo e NO (de 0,29 ± 0,1 μM para 0,19 ± 0,1 μM, p=0,003), o TNF-α (de 71,0 ± 22,3 ng/ml para 50,1 ± 2,1 ng/ml, p=0,043), interleucina-6 (de 121,6 ± 3,0 pg/ml para 111,1 ± 5,6 pg/ml, p=0,008). Do mesmo modo, o aumento do número de células infiltrativas no tecido uveal em seções histológicas foi significativamente inibido pelo licopeno, a pontuação inflamatória diminuiu de 2,0 ± 0,0 para 0,4 ± 0,5, p=0,001. Embora, não tenha sido estatisticamente significativo, o licopeno reduziu a contagem de células infiltrativas e a concentração de proteínas no humor aquoso. Conclusões: Estes resultados sugerem que o licopeno pode ter efeitos benéficos no tratamento da inflamação ocular, através dos seus efeitos anti-inflamatórios e antioxidantes.

Pneumatosis intestinalis after etoposide-based chemotherapy in a patient with metastatic small cell lung cancer: successful conservative management of a rare condition / Pneumatose intestinal após quimioterapia com etoposídeo em paciente com câncer de pulmão de pequenas células: sucesso com conduta conservadora em uma condição rara

ABSTRACT A 69-year-old male patient, smoker, was diagnosed with small cell lung cancer metastatic to lung, liver and central nervous system. He received chemotherapy with carboplatin AUC 5 on day 1 and etoposide 100mg/m2 on days 1, 2 and 3. During the first cycle, the patient presented with febrile neutropenia and abdominal distension. Chest, abdomen and pelvis computed tomography scan was performed and detected gas dissecting the wall of sigmoid colon extending to the mesosigmoid. Patient had no abdominal pain, nausea, vomiting, and on physical examination he had no peritoneal irritation, tachycardia or hemodynamic instability compatible with perforation or acute abdomen. Therefore, the radiological finding was interpreted as pneumatosis intestinalis caused by chemotherapy with etoposide. Pneumatosis resolved after continuous oxygen therapy. The second cycle was administered after a complete resolution of the clinical condition and etoposide dose was reduced by 30%. The patient experienced a remarkable evolution.

RESUMO Paciente do gênero masculino, 69 anos, fumante, diagnosticado com câncer de pulmão de pequenas células, metastático para pulmão, fígado e sistema nervoso central. Foi administrada quimioterapia com carboplatina AUC 5 no dia 1 e etoposídeo 100mg/m2 nos dias 1, 2 e 3. Durante o primeiro ciclo, o paciente apresentou neutropenia febril e distensão abdominal. Tomografias de tórax, abdome e pelve detectaram gás dissecando a parede do cólon sigmoide, com extensão para o mesossigmoide. O paciente não apresentava dor abdominal, náusea, vômito e não tinha sinais de irritação peritoneal, taquicardia ou instabilidade hemodinâmica compatíveis com perfuração ou abdome agudo. O achado radiológico foi interpretado como pneumatose intestinal causada por etoposídeo. A resolução do quadro ocorreu após suplementação de oxigênio. O segundo ciclo foi administrado após resolução completa do quadro, com redução da dose do quimioterápico em 30%. O paciente evoluiu de forma bastante satisfatória.

Indução da dor pelo quimioterápico docetaxel em mulheres com câncer de mama / Pain induction by chemotherapy medication docetaxel in women with breast cancer

Resumo Objetivo Descrever a frequência, características, localização, intensidade da dor em pacientes com câncer de mama em uso do quimioterápico Docetaxel. Métodos Estudo longitudinal realizado com 17 mulheres com câncer de mama em tratamento com Docetaxel. As pacientes foram avaliadas durante três ciclos da quimioterapia quanto à dor, utilizando-se os instrumentos Questionário McGill de Dor (Br-MPQ) e Brief Pain Inventory (BPI). Utilizou-se a correlação de Spearman e o teste de Mann-Whitney. Resultados Houve aumento na média da dor em todas as variáveis do BPI. Quando comparados os valores do Pain Rating Index (PRI) total foram verificados respectivamente 0,20; 0,33 e 0,24 na primeira, segunda e terceira avaliações, sendo encontrada correlação entre a intensidade da dor e a interferência em todas as atividades do cotidiano no BPI na segunda avaliação. Conclusão Houve aumento na ocorrência da dor, comprometendo as atividades diárias de vida das mulheres participantes.

Abstract Objective To describe the frequency, characteristics, location, pain intensity in breast cancer patients using the chemotherapy medication Docetaxel. Methods Longitudinal study involving 17 women with breast cancer under treatment using Docetaxel. The patients’ pain was assessed during three chemotherapy cycles, using the tools McGill Pain Questionnaire (Br-MPQ) and the Brief Pain Inventory (BPI). Spearman’s correlation and the Mann-Whitney test were used. Results The mean pain score increased in all variables of the BPI. When comparing the total coefficients on the Pain Assessment Index, 0.20; 0.33 and 0.24 were found in the first, second and third assessment, showing a correlation between the pain intensity and the interference in all daily activities on the BPI for the second assessment. Conclusion The occurrence of pain increased, compromising the participating women’s activities of daily living.

DRESS syndrome in ophthalmic patients / Síndrome DRESS em pacientes oftalmológicos

ABSTRACT Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal adverse drug reaction associated with skin rash, fever, eosinophilia, and multiple organ injury. A number of pharmacological agents are known to cause DRESS syndrome such as allopurinol, anticonvulsants, vancomycin, trimethoprime-sulfamethoxazole, and pyrimethamine-sulfadiazine. Here, we describe two patients who developed DRESS syndrome during ocular treatment. The first case was being treated for late postoperative endophthalmitis with topical antibiotics, intravenous cephalothin, meropenem, and intravitreal injection of vancomycin and ceftazidime before symptoms developed. We were unable to identify the causal drug owing to the large number of medications concurrently administered. The second case presented with DRESS syndrome symptoms during ocular toxoplasmosis treatment. In this case, a clearer association with pyrimethamine-sulfadiazine was observed. As a result of the regular prescription of pharmacological agents associated with DRESS syndrome, ophthalmologists should be aware of the potentially serious complications of DRESS syndrome.

RESUMO Síndrome DRESS (drug reaction with eosinophilia and systemic symptoms) é uma reação adversa a medicamentos rara e potencialmente fatal, associada à rash cutâneo, febre, eosinofilia e lesão de múltiplos órgãos. Algumas drogas podem desencadeá-la, como: alopurinol, anticonvulsivantes, vancomicina, sulfametoxazol-trimetoprim, sulfadiazina-pirimetamina, entre outras. Descrevemos dois casos que desenvolverem DRESS síndrome durante tratamento ocular. O primeiro caso apresentou os sintomas durante tratamento para endoftalmite pós-operatória tardia com antibióticos tópicos, cefalotina e meropenem intravenosos e injeção intravítrea de vancomicina e ceftazidima; não podemos identificar a droga causadora, pois múltiplas medicações foram utilizadas. O segundo caso desenvolveu os sintomas durante tratamento clássico para toxoplasmose ocular, então a associação com sulfadiazina-pirimetamina foi mais clara. Como muitos oftalmologistas prescrevem regularmente drogas que podem desencadear a síndrome DRESS, esse diagnóstico deve ser lembrado já que pode levar a sérias complicações.

Enoftalmia causada por uso tópico unilateral de Bimatoprost / Unilateral enophthalmos induced by the unilateral use of topical Bimatoprost

RESUMO O autor descreve o caso de uma paciente que apresenta o olho direito com o sulco palpebral profundo e enoftalmia deste lado, tratado durante uma década com Bimatoprost tópica. Concluem que os achados clínicos são provavelmente efeitos colaterais do medicamento.

ABSTRACT The author describes a case report of a patient with unilateral enophthalmia and deep palpebral sulcus probably induced by the topical use of Bimatoprost on the side of the collateral effects described.