Treatment of noninfectious uveitis / Tratamento das uveítes não-infecciosas

ABSTRACT Uveitis is a broad term that refers to a large group of eye disorders categorized by intraocular inflammation, a leading cause of visual impairment. Historically, treatment of noninfectious uveitis has depended on corticosteroid drugs. Owing to the myriad of side effects caused by corticosteroids, immunomodulatory therapy has become the preferred treatment for chronic noninfectious intraocular inflammation. Recently, biological response modifiers have established a new era in uveitis therapy, with the range of targets continuing to expand. In this review, we aimed to convey up-to-date information on the treatment of noninfectious uveitis to the general ophthalmologist.

RESUMO Uveíte é um termo amplo utilizado para denominar várias desordens categorizadas como inflamação intraocular, uma causa importante de deficiência visual. Historicamente, o tratamento das uveítes não infecciosas baseou-se no uso de corticosteróides. Devido aos diversos efeitos colaterais do uso de corticosteróides a longo prazo, a terapia imunomoduladora é indicada no tratamento das uveítes não infecciosas crônicas. A introdução dos medicamentos biológicos estabeleceu uma nova era no tratamento das uveítes, com constante desenvolvimento de novas drogas. O objetivo desta revisão é trazer informações atuais sobre tratamento das uveítes não infecciosas para a prática clínica do oftalmologista geral.

The mechanism and treatment strategies of SARS-CoV-2 mediated inflammatory response / 生物医学工程学杂志

Since the emergence of novel coronavirus pneumonia in late 2019, it has quickly spread to many countries and regions around the world, causing a significant impact on human beings and society, posing a great threat to the global public health system. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was highly infectious, and some complications emerged rapidly in some patients, including acute respiratory distress syndrome, and multiple organ failure. The virus could trigger a series of immune responses, which might lead to excessive immune activation, thereby bringing about the immune system imbalance of the body. Up to now, there was no specific antiviral drug, and we conjectured that immunomodulatory therapy might play an essential part in the treatment of coronavirus disease 2019 (COVID-19) as adjuvant therapy. Therefore, we analyzed the possible mechanism of immune imbalance caused by the new coronavirus, and summarized the immunotherapeutic means of COVID-19 based on the mechanisms, to provide some reference for follow-up research and clinical prevention and treatment of COVID-19.

The severe COVID-19: A sepsis induced by viral infection? And its immunomodulatory therapy / 中华创伤杂志(英文版)

COVID-19 is known for its magical infectivity, fast transmission and high death toll based on the large number of infected people. From the perspective of the clinical manifestation, autopsy examination and pathophysiology, the essence of COVID-19 should be viewed as a sepsis induced by viral infection, and has the essential characteristics as sepsis induced by other pathogens. Therefore, in addition to etiological and supportive treatment, immunomodulatory therapy is also appropriate to severe COVID-19. Although there is still a lack of consensus on immunotherapy for sepsis so far, relatively rich experiences have been accumulated in the past decades, which will help us in the treatment of severe COVID-19. This article will elaborate immunotherapy of sepsis, though it may not be consistent.

Microglia and Autism Spectrum Disorder: Overview of Current Evidence and Novel Immunomodulatory Treatment Options

Autism spectrum disorder is a rapidly increasing heterogeneous neurodevelopmental syndrome, remarked by persistent deficit in social communication, and restricted, repetitive patterns of behavior and interest. Lately, maternal immune activation and micgroglial dysfunction in the developing brain have been gaining mounting evidence and leading to studies of various novel agents as potential treatment options. A few immunomodulatory treatment options—luteolin, minocycline, suramin, vitamin D, gut microbiota—are discussed in the current article, regarding the current understanding of their mechanisms and evidence for potential clinical use. More studies are warranted to understand their exact mechanisms of action and to verify efficacy and safety in human subjects.

Progresses of immunomodulatory therapy in sever acute pancreatitis / 中华危重病急救医学

Severe acute pancreatitis (SAP) is accompanied with complex pathogenic course and high mortality. The imbalance of immune response is an important cause which leads the SAP patients to the severe situation and even death. The immunomodulatory therapy can regulate the imbalance of inflammation, alleviate SAP-associated organ injury, and improve the prognosis of patients. Previous immunomodulatory therapy had some problems, such as single-object and simple-method. In recent years, some new methods of immunomodulatory therapy, such as regulating the apoptosis and mature of immune cells, applying of mesenchymal stem cells (MSCs) and multi-regulation methods, provide some new ideas and hopes for SAP therapy. This paper reviewed the history and recent research progresses of SAP immunomodulatory therapy.

Progresses of immunomodulatory therapy in sever acute pancreatitis / 中华危重病急救医学

Severe acute pancreatitis (SAP) is accompanied with complex pathogenic course and high mortality. The imbalance of immune response is an important cause which leads the SAP patients to the severe situation and even death. The immunomodulatory therapy can regulate the imbalance of inflammation, alleviate SAP-associated organ injury, and improve the prognosis of patients. Previous immunomodulatory therapy had some problems, such as single-object and simple-method. In recent years, some new methods of immunomodulatory therapy, such as regulating the apoptosis and mature of immune cells, applying of mesenchymal stem cells (MSCs) and multi-regulation methods, provide some new ideas and hopes for SAP therapy. This paper reviewed the history and recent research progresses of SAP immunomodulatory therapy.

Effects of testosterone on heart function following heart failure after myocardial infarction in rats / 中国综合临床

Objective To investigate the effects of low dose testosterone on heart function,and ventricular remodeling in male rats with postinfarction congestive heart failure(CHF).Methods Sixty SD rats were undergone surgery,of which,45 rats were performed coronary artery ligation and other 15 were sham group (PS group).Six weeks later,left ventricular function of survived rats was examined by echocardiography,and LVEF≤45％ was defined as the standard of successful CHF model.All survived model rats were randomly divided into 2 groups:TU group(n =16) treated with TU 5 mg/kg per 2 weeks intramuscular injection;placebo (PL) group (n =16) treated with PL.Mter treatment for 12 weeks,left ventricular ejection fraction(LVEF) was assessed by echocardiography again.Serum testosterone level was determined by radioimmunoassay.The expression of tumor necrosis factor-or (TNF-α) mRNA and matrix metalloproteinase (MMP)-9mRNA in myocardial tissue was measured by RT-PCR.Results In male post-myocardial infarction rats,serum testosterone level and LVEF were decreased significantly than PS group(P ＜ 0.05),and the expression of TNF-α mRNA and MMP-9 mRNA in myocardial tissue was increased significantly than PS group (P ＜ 0.05).Mter low dose TU therapy,LVEF of rats in TU group improved significantly(P ＜0.05),and the expression of TNF-α mRNA and MMP-9 mRNA in myocardial tissue was reduced significantly (P ＜ 0.05).Meanwhile,the mortality was decreased (P ＜ 0.05).Conclusion Low dose testosterone therapy can restore the inflammatory imbalance and suppress the ventricular remodeling in male post-myocardial infarction rats and improve left ventricular function,as well as reduce mortality.

Stevens-Johnson syndrome / toxic epidermal necrolysis: an Asia-Pacific perspective

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCAR) to drugs which are associated with significant morbidity and mortality. High risk drugs in Asia are similar to those reported worldwide. Human leukocyte antigen (HLA)-related risk alleles for carbamazepine and allopurinol SCAR are unique to Asians. Although prognostic scoring systems like the SCORTEN have been used for more than a decade, pitfalls and caveats need to be recognized, in particular in patients with multiple medical co-morbidities and systemic features in SJS/TEN. In centres without a tertiary Burns Centre, SJS/TEN patients can still be managed successfully in general and dermatology wards with well-executed supportive/nursing care. Controversy remains regarding the effectiveness of immunomodulation in reducing SJS/TEN morbidity, mortality and hastening re-epithelialization. Despite paucity of robust evidence, intravenous immunoglobulins and ciclosporin remain the most commonly used modalities worldwide. Acute and long-term ocular effects are an important source of morbidity for which emerging ophthalmic therapies appear promising. Quality of life issues have now become an important outcome in patients with SJS/TEN as they often impact survivors' future attitudes towards pharmacotherapy. Even though pharmacogenetic testing for high-risk drugs appears to be the panacea for preventing carbamazepine- and allopurinol-induced SJS/TEN in ethnic Asians, many issues remain before health regulators in our region can conclusively determine whether testing should be made mandatory or highly recommended as standard of care.

Classical immunomodulatory therapy in multiple sclerosis: how it acts, how it works / Terapêutica imunomoduladora clássica na esclerose múltipla: como atua, como funciona

Interferon beta (IFNβ) and glatiramer acetate (GA) were the first immunomodulators approved to the treatment of relapsing-remitting multiple sclerosis (MS) and clinically isolated syndromes. Despite the enlargement of the therapeutic armamentarium, IFNβ and GA remain the most widely drugs and the therapeutic mainstay of MS. OBJECTIVE: To review the mechanisms of action of IFNβ and GA and main clinical results in MS. RESULTS: IFNβ modulates T and B-cell activity and has effects on the blood-brain barrier. The well proved mechanism of GA is an immune deviation by inducing expression of anti-inflammatory cytokines. Some authors favor the neuroprotective role of both molecules. Clinical trials showed a 30 percent reduction on the annualized relapse rate and of T2 lesions on magnetic resonance. CONCLUSION: Although the precise mechanisms how IFNβ and GA achieve their therapeutics effects remain unclear, these drugs have recognized beneficial effects and possess good safety and tolerability profiles. The large clinical experience in treating MS patients with these drugs along almost two decades deserves to be emphasized, at a time where the appearance of drugs with more selective mechanisms of action, but potentially less safer, pave the way to a better selection of the most appropriate individualized treatment.

O interferão beta (IFNβ) e o acetato de glatirâmero (GA) foram os primeiros imunomoduladores aprovados para o tratamento da esclerose múltipla (EM) surto-remissão e doentes com síndromes clinicamente isoladas. Apesar do alargamento do armamentário terapêutico, o IFNβ e o GA continuam a ser os medicamentos mais usados na EM. OBJETIVO: Rever os mecanismos de acção do IFNβ e do GA e os principais resultados na clínica. RESULTADOS: O IFNβ modula a actividade das células T e B e tem efeitos sobre a barreira hemato-encefálica. O mecanismo melhor comprovado do GA é o desvio imune através da indução da expressão de citocinas. Alguns autores favorecem ainda um papel neuroprotetor para ambos. Os ensaios clínicos mostraram diminuição da taxa anualizada de surtos de 30 por cento e das lesões em T2 na ressonância magnética. CONCLUSÃO: Embora os mecanismos pelos quais o IFNβ e o GA atingem os seus efeitos terapêuticos continuem a ser pouco claros, estes fármacos possuem efeitos benéficos reconhecidos e bons perfis de segurança e tolerabilidade. A grande experiência clínica no tratamento da EM com estes fármacos ao longo de quase duas décadas merece ser destacada, numa altura em que o aparecimento de novos fármacos com mecanismos de acção mais seletivos, mas potencialmente menos seguros, possibilitarão melhor seleção e individualização do tratamento.

Influence of treatment in multiple sclerosis dysability: an open, retrospective, non-randomized long-term analysis / Influência do tratamento na incapacidade da esclerose múltipla: estudo aberto, retrospectivo e não randomizado em longo prazo

The efficacies of immunosuppressive (IMS) and immunomodulatory (IMM) drugs for multiple sclerosis (MS) have been reported in several studies. These agents can reduce relapse rates and lesions observed by magnetic resonance imaging studies. However, the effect of these medications in disability progression over 4 years is rarely examined. OBJECTIVE: To study the disabilities associated with MS patients after a long time period and to analyze the therapeutic influence of different types of treatments in patient disease progression. METHOD: This is an open, uncontrolled, non-randomized, retrospective study of the disease progression using the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS) in 155 cases of MS, which were 76 percent female with a mean age of onset of 30.21±9.70. The follow-up period was 115.39±88.08 months (median 92, 3 to 447 months). These cases were submitted to the following 277 different therapeutic procedures: 62 without IMS or IMM therapy (SYT) (just corticosteroids), 53 with azathioprine (AZA), 53 interferon-β (IFNβ)-1b 250 µg (BET), 55 IFNβ-1a 22 µg (R22), 19 IFNβ-1a 30 µg (AVO), 15 IFNβ-1a 44 µg (R44), 15 glatiramer acetate (COP) 20 mg, and 5 cases with mitoxantrone (MIT). RESULTS: The median EDSS group was 2.00 (0 to 5.5, mean 1.89±1.52) at the onset of each treatment and 2.50 (0 to 9, mean 3.06±2.18) at the end. The median initial MSSS was 3.34 (0.25 to 9.50, mean 3.94±2.91) and the final medial was 3.90 (0.05 to 9.88, mean 4.02±2.78). The EDSS between initial and final score for the whole group had statistically significant progression, as well as for the sub-groups SYT, AZA, BET and R22. No statistically significance difference was found in the MSSS between initial and final scores in the whole group or treatment sub-groups. The variation between the initial and final EDSS and MSSS among the types of treatments found no statistical significance...

A eficácia das medicações imunossupressivas (IMS) e imunomoduladoras (IMM) na esclerose múltipla (MS) tem sido relatada em diversos estudos. Essas medicações podem reduzir o número de surtos e de lesões observadas nos estudos de ressonância magnética. Entretanto, o efeito dessas medicações na progressão da incapacidade em período acima de quatro anos é raramente estudado. OBJETIVO: Estudar a incapacidade associada à MS em longo prazo e analisar os benefícios dos diferentes tipos de tratamento na progressão da doença. MÉTODO: Estudo aberto e retrospectivo da progressão da incapacidade utilizando a escala expandida do grau de incapacidade (EDSS) e o escore da gravidade da esclerose múltipla (MSSS) em 155 casos de MS, sendo 76 por cento do sexo feminino, idade média no início da doença 30,21±9,70 anos e período médio de seguimento 115,39±77,08, mediana 92 (3 a 447) meses. Os casos foram submetidos a 277 tipos diferentes de tratamentos: 62 casos não usaram IMS ou IMM, somente corticosteróides (SYT); 53 com azatioprina (AZA); 53 com interferon-β (IFNβ)-1b 250 µg (BET); 55 com IFNβ-1a 22 µg (R22); 19 com IFNβ-1a 30 µg (AVO); 15 com IFNβ-1a 44 µg (R44); 15 com acetato de glatiramer (COP) 20 mg, e 5 casos com mitoxantrone (MIT). RESULTADOS: A mediana do EDSS do grupo foi 2,0 (0 a 5,5, média total do grupo foi 1,89±1,52) no início de cada tratamento e 2,50 (0 a 9, média de 3,06±2,18) no fim. A mediana inicial da MSSS foi 3,34 (0,25 a 9,50, média 3,94±2,91) e a final 3,90 (0,05 a 9,88, média 4,02±2,78). O EDSS entre o início e o fim do tratamento do grupo mostrou progressão estatisticamente significante e também para os subgrupos SYT, AZA, BET e R22. Não foi encontrada diferença estatística no MSSS entre o início e fim do tratamento no grupo total ou nos subgrupos. Não foi encontrada diferença estatisticamente significante entre a variação inicial e final do EDSS e MSSS entre os diversos subgrupos de tratamento...