Ongoing living update of potential COVID-19 therapeutics: summary of rapid systematic reviews - 18 December 2020

This is the thirteenth edition of this summary of rapid systematic reviews, which includes the results of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 58 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, pregnant women, those with immune conditions, etc.

Ongoing living update of potential COVID-19 therapeutics: summary of rapid systematic reviews - 30 November 2020

This is the twelfth edition of this summary of rapid systematic reviews, which includes the results of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 58 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, expectant mothers, those with immune conditions, etc.

Ongoing living update of potential COVID-19 therapeutics: summary of rapid systematic reviews - 13 November 2020

This is the twelfth edition of this summary of rapid systematic reviews, which includes the results of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 58 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, expectant mothers, those with immune conditions, etc.

Ongoing living update of potential COVID-19 therapeutics: summary of rapid systematic reviews - 13 January 2021

This is the fourteenth edition of this database of evidence on potential therapeutic options for COVID-19, in which 68 therapeutic options are examined. This information will help investigators, policy makers, and prescribers navigate the flood of relevant data to ensure that management of COVID-19, at both individual and population levels, is based on the best available knowledge. This resource will be continually updated as more research is released into the public space.

Uso de fármacos anticorpos monoclonais, imunomoduladores e anti-inflamatórios no tratamento da infecção por COVID-19 / Use of monoclonal antibodies, immunomodulators, and anti-inflammatory drugs in the treatment of COVID-19

O objetivo deste estudo foi realizar o levantamento bibliográfico de artigos científicos e ensaios clínicos sobre a utilização de anticorpos monoclonais, imunomoduladores e anti-inflamatórios como possíveis alternativas terapêuticas para uso em pacientes com COVID-19, com ênfase nos mecanismos de ação e resultados de ensaios clínicos. Foram analisados artigos obtidos na base de dados MEDLINE® e ensaios clínicos disponíveis no site ClinicalTrials no período de 6 de abril a 6 de maio de 2020. Os ensaios realizados com os fármacos apresentados nesta revisão bibliográfica sugerem a viabilidade de uso de algumas dessas drogas como alternativas para tratamento da COVID-19. No entanto, observou-se que, em função do número reduzido de participantes dos estudos disponíveis, é indispensável a continuidade de pesquisas e dos ensaios clínicos com esses medicamentos, para estimar a eficácia dessas drogas no tratamento do SARS-CoV-2, contra o qual ainda não há terapia específica

The objective of this study was to carry out a bibliographic survey of scientific articles and current clinical trials on the use of monoclonal antibodies, immunomodulators, and anti-inflammatories as possible therapeutic alternatives for use in patients with COVID-19, highlighting their mechanisms of action and results of clinical trials. Articles from the MEDLINE® database and clinical trials available on the ClinicalTrials website were analyzedThe tests performed with the drugs presented in this bibliographic review suggest the feasibility of using some of these drugs as treatment alternatives for COVID-19. However, it was observed that the small samples evaluated in these tests make it imperative to proceed with research and clinical trials with these drugs to provide greater evidence of the effectiveness of these drugs in the treatment of the disease caused by SARS-CoV-2, for which there is no specific therapy so far.

Avaliação da suplementação diária de ácidos graxos poli-insaturados de ômega-3 e aspirina em baixa dosagem no tratamento de periodontite agressiva generalizada: estudos clínicos controlados randomizados / Evaluation of omega-3 polyunsaturated fatty acids daily supplementation plus low-dose aspirin to treat generalized aggressive periodontitis: randomized controlled clinical trials

A destruição periodontal resulta principalmente da resposta inflamatória exacerbada do hospedeiro frente ao desafio bacteriano. Por isso, pesquisas envolvendo a modulação da resposta do hospedeiro têm sido desenvolvidas com o objetivo de facilitar a resolução da inflamação, bem como promover reparação tecidual e estabilidade periodontal. Recentemente, o uso de ácidos graxos poli-insaturados de ômega-3 (AGP Ω-3) e ácido acetilsalicílico (AAS) foi relacionado à produção de mediadores lipídicos mais bioativos e à melhores resultados clínicos no tratamento de periodontite crônica. Desse modo, pesquisas envolvendo modulação das respostas inflamatórias de portadores de periodontite agressiva (PAg) podem ser de grande valia. Assim, o objetivo dos presentes estudos clínicos controlados randomizados foi avaliar a utilização da suplementação de 900 mg AGP Ω-3 e 100 mg de AAS por 180 dias como adjuvantes ao tratamento de PAg generalizada (PAgG). (1) Selecionou-se 38 pacientes com PAgG os quais receberam debridamento subgengival associado a AGP Ω-3 e AAS (n=19) ou placebo (n=19). Ambos os grupos apresentaram diminuição (p<0,05) em todos os parâmetros clínicos avaliados, bem como em IL-1ß, sem diferença entre os tratamentos (p>0,05). O nível de TIMP-2 diminuiu significantemente no grupo controle, porém se manteve estável no grupo teste. Concluiu-se que a nova terapia proposta não trouxe benefícios clínicos no tratamento não-cirúrgico de PAgG. (2) Selecionou-se 34 pacientes com PAgG previamente submetidos à terapia básica que apresentavam bolsas residuais e foram submetidos à cirurgia de acesso para raspagem e alisamento radicular associado a AGP Ω-3 e AAS (n=17) ou placebo (n=17). Após 6 meses, ambos os grupos obtiveram diminuição na PS (p<0,05), porém somente o grupo teste obteve ganho no NIC na comparação intergrupo (p=0,02), assim como apresentou menor recessão gengival (p=0,03), diminuição da hipersensibilidade dentinária (p=0,01), menor consumo de analgésicos (p=0,02) e diminuição intragrupo de IL-10 (p<0,05). Concluiu-se que a nova terapia proposta trouxe benefícios clínicos no tratamento de bolsas residuais de pacientes com PAgG(AU)

Periodontal destruction results mainly from the exacerbated host inflammatory response to the bacterial challenge. For this reason, research involving the modulation of host response has been developed aiming to facilitate the resolution of inflammation, as well as to promote tissue repair and periodontal stability. Recently, the use of omega-3 polyunsaturated fatty acids (Ω-3 PUFA) and low-dose acetylsalicylic acid (ASA) was related to the production of enhanced lipidic mediators and to better clinical outcomes in the treatment of chronic periodontitis. Thus, the aim of the present randomized controlled clinical trials was to evaluate the use of 900 mg Ω-3PUFA and 100 mg ASA for 180 days as adjuvants to the treatment of generalized aggressive periodontitis (GAgP). (1) Thirty-eight GAgP patients were submitted to subgingival debridement associated with Ω-3 PUFA and ASA (n=19) or placebo (n=19). Both groups showed a statistically significant decrease (p<0.05) in all clinical parameters, as well as a decrease in IL-1ß, with no difference between treatments (p>0.05). The TIMP-2 level significantly decreased in the control group and remained stable in the test group. It was concluded that the proposed new therapy did not bring clinical benefits in the non-surgical treatment (NST) of GAgP. (2) Thirty-four GAgP patients previously submitted to NST with residual pockets were selected and underwent open flap debridement associated with Ω-3 PUFA 3 and ASA (n=17) or placebo (n=17). After 6 months, both therapies led to decreased PD (p>0.05), but only the test group had CAL gain in the intergroup comparison (p=0,02), as well as presented less gingival recession (p=0,03), decreased dentin hypersensitivity (p=0,01), lower consumption of analgesics (p=0,02) and significant intragroup reduction of IL-10 (p<0.05). It was concluded that the proposed new therapy brought clinical benefits in the surgical treatment of GAgP patient(AU)

Preclinical efficacy against toxic activities of medically relevant Bothrops sp. (Serpentes: Viperidae) snake venoms by a polyspecific antivenom produced in Mexico / Eficacia de un antiveneno poliespecífico producido en México para neutralizar, a nivel preclínico, las actividades tóxicas de venenos de Bothrops sp (Serpentes: Viperidae) de importancia médica

Abstract:The assessment of the preclinical neutralizing ability of antivenoms in Latin America is necessary to determine their scope of efficacy. This study was aimed at analyzing the neutralizing efficacy of a polyspecific bothropic-crotalic antivenom manufactured by BIRMEX in Mexico against lethal, hemorrhagic, defibrinogenating and in vitro coagulant activities of the venoms of Bothrops jararaca (Brazil), B. atrox (Perú and Colombia), B. diporus (Argentina), B. mattogrossensis (Bolivia), and B. asper (Costa Rica). Standard laboratory tests to determine these activities were used. In agreement with previous studies with bothropic antivenoms in Latin America, a pattern of cross-neutralization of heterologous venoms was observed. However, the antivenom had low neutralizing potency against defibrinogenating effect of the venoms of B. atrox (Colombia) and B. asper (Costa Rica), and failed to neutralize the in vitro coagulant activity of the venom of B. asper (Costa Rica) at the highest antivenom/venom ratio tested. It is concluded that, with the exception of coagulant and defibrinogenating activities of B. asper (Costa Rica) venom, this antivenom neutralizes toxic effects of various Bothrops sp venoms. Future studies are necessary to assess the efficacy of this antivenom against other viperid venoms. Rev. Biol. Trop. 65 (1): 345-350. Epub 2017 March 01.

ResumenEs necesario estudiar a nivel preclínico la capacidad neutralizante de los antivenenos producidos en América Latina, para conocer su espectro de cobertura. En este estudio se analizó la eficacia preclínica de un antiveneno poliespecífico botrópico-crotálico producido por BIRMEX, en México, para neutralizar los efectos letal, hemorrágico, desfibrinogenante y coagulante in vitro de los venenos de Bothrops jararaca (Brasil), B. atrox (Perú y Colombia), B. diporus (Argentina), B. mattogrossensis (Bolivia) y B. asper (Costa Rica). Se emplearon metodologías de laboratorio estándar en los análisis. En consonancia con estudios anteriores con diversos antivenenos botrópicos en América Latina, se observó un amplio patrón de neutralización de estos venenos heterólogos en la mayoría de los efectos estudiados. Sin embargo, el antiveneno mostró una baja capacidad neutralizante contra el efecto desfibrinogenante de los venenos de B. atrox (Colombia) y B. asper (Costa Rica) y no neutralizó la actividad coagulante in vitro del veneno de B. asper (Costa Rica) a la máxima razón antiveneno/ veneno empleada.

Pulsed ultrasound therapy accelerates the recovery of skeletal muscle damage induced by Bothrops jararacussu venom

We studied the effect of pulsed ultrasound therapy (UST) and antibothropic polyvalent antivenom (PAV) on the regeneration of mouse extensor digitorum longus muscle following damage by Bothrops jararacussu venom. Animals (Swiss male and female mice weighing 25.0 ± 5.0 g; 5 animals per group) received a perimuscular injection of venom (1 mg/kg) and treatment with UST was started 1 h later (1 min/day, 3 MHz, 0.3 W/cm², pulsed mode). Three and 28 days after injection, muscles were dissected and processed for light microscopy. The venom caused complete degeneration of muscle fibers. UST alone and combined with PAV (1.0 mL/kg) partially protected these fibers, whereas muscles receiving no treatment showed disorganized fascicules and fibers with reduced diameter. Treatment with UST and PAV decreased the effects of the venom on creatine kinase content and motor activity (approximately 75 and 48%, respectively). Sonication of the venom solution immediately before application decreased the in vivo and ex vivo myotoxic activities (approximately 60 and 50%, respectively). The present data show that UST counteracts some effects of B. jararacussu venom, causing structural and functional improvement of the regenerated muscle after venom injury.

Immunomodulatory effects of human amniotic membrane-derived mesenchymal stem cells

Human amniotic membrane-derived mesenchymal stem cells (hAM-MSCs) are capable of differentiating into several lineages and possess immunomodulatory properties. In this study, we investigated the soluble factor-mediated immunomodulatory effects of hAM-MSCs. Mitogen-induced peripheral blood mononuclear cell (PBMC) proliferation was suppressed by hAM-MSCs in a dose-dependent manner as well as hAM-MSC culture supernatant. Moreover, interferon-gamma and interleukin (IL)-17 production significantly decreased from PBMC, whereas IL-10 from PBMCs and transforming growth factor beta (TGF-beta) production from hAM-MSCs significantly increased in co-cultures of hAM-MSCs and PBMCs. Production of several MSC factors, including hepatocyte growth factor (HGF), TGF-beta, prostaglandin E2 (PGE2), and indoleamine 2, 3 dioxygenase (IDO), increased significantly in hAM-MSCs co-cultured with PBMCs. These results indicate that the immunomodulatory effects of hAM-MSCs may be associated with soluble factors (TGF-beta, HGF, PGE2, and IDO), suggesting that hAM-MSCs may have potential clinical use in regenerative medicine.

Cholera toxin: A paradigm of a multifunctional protein.

Cholera toxin (CT) was discovered exactly half a century ago by S.N. De. We have come a long way since this epoch-making discovery. Retrospectively, science had to wait a long time since Koch’s prediction of the existence of a toxin, and its actual discovery by De. CT is not just another enterotoxin that causes the signs and symptoms of the dreaded disease, cholera. It is unique in many respects, starting from its structure to its functions. CT is a multifunctional protein that is capable of influencing the immune system in many ways. It not only has remarkable adjuvant properties, but also acts as an anti-inflammatory agent, by modulating specific signal transduction pathways. Its immunomodulatory properties can be harnessed for treatment of various autoimmune disorders, and have shown great promise in the area of immunotherapeutics. CT can truly be considered as a paradigm of a multifunctional protein.

The interaction between Histoplasma capsulatum cell wall carbohydrates and host components: relevance in the immunomodulatory role of histoplasmosis

Histoplasma capsulatum is an intracellular fungal pathogen that causes respiratory and systemic disease by proliferating within phagocytic cells. The binding of H. capsulatum to phagocytes may be mediated by the pathogen's cell wall carbohydrates, glucans, which consist of glucose homo and hetero-polymers and whose glycosydic linkage types differ between the yeast and mycelial phases. The ±-1,3-glucan is considered relevant for H. capsulatum virulence, whereas the ²-1,3-glucan is antigenic and participates in the modulation of the host immune response. H. capsulatum cell wall components with lectin-like activity seem to interact with the host cell surface, while host membrane lectin-like receptors can recognize a particular fungal carbohydrate ligand. This review emphasizes the relevance of the main H. capsulatum and host carbohydrate-driven interactions that allow for binding and internalization of the fungal cell into phagocytes and its subsequent avoidance of intracellular elimination.

Auto-imunidade ANCA (Anticorpo Anti-Citoplasma de Neutrófilos) positiva induzida por propiltiouracil: relato de caso e revisão da literatura / Antineutrophil Cytoplasmic Antibody (Anca)-Associated autoimmune disease induced by propylthiouracil

A terapêutica com drogas antitireoidianas pode ser acompanhada de efeitos colaterais. Propiltiouracil (PTU) pode induzir vasculites anticorpo anti-citoplasma de neutrófilos (ANCA) positivas, na maioria das vezes relacionadas ao subtipo mieloperoxidase (ANCA-MPO). O nosso objetivo é relatar o caso de uma paciente com doença de Graves que desenvolveu auto-imunidade induzida por PTU, com manifestações cutâneas, pulmonares e renais, associadas à positividade do ANCA. O exame anátomo-patológico pulmonar revelou hemorragia difusa e a biópsia renal demonstrou glomeruloesclerose segmentar e focal. Foi tratada com pulsoterapia com corticóides e ciclofosfamida, com boa evolução clínica. Este caso enfatiza a necessidade de detecção e tratamento precoce deste efeito adverso relativamente raro do PTU.

Antithyroid drugs sometimes cause severe complications. Propylthiouracil (PTU) can be associated to ANCA positive vasculitis, most often related to myeloperoxidase subtype (ANCA-MPO). Our objective is to describe a female patient with Graves' disease, who developed PTU induced-autoimmune disease, with cutaneous, pulmonary, and renal lesions, associated with ANCA. Histopathological examination revealed diffuse pulmonary hemorrhage, and focal segmental glomerulosclerosis at the kidney biopsy. She was treated with systemic corticosteroid therapy and cyclophosphamide, with clinical improvement. This case highlights the need for greater awareness of this relatively rare adverse effect of propylthiouracil.

IgG antibody profile to c-terminal region of Plasmodium vivax merozoite surface protein-1 in Thai individuals exposed to malaria.

Naturally acquired immune response to C-terminal region of Plasmodium vivax merozoite surface protein1 (PvMSP1) in 200 individuals with recent clinical episodes of malaria from malaria endemic areas along Thai-Myanmar border in the west and Thai-Cambodia border in the east of Thailand was evaluated by enzyme-linked immunosorbent assay (ELISA). The anti-PvMSP1-IgG antibody was observed in 110 individuals (55%). Among IgG responders, IgG1 coexpressed with IgG3 were the predominant subclasses. The levels of anti-PvMSP1 total IgG, IgG1 and IgG3 antibody response seem to be increased with age although no detectable significant correlation was found (r = 0.004, p = 0.484 for total IgG; r = 0.035, p = 0.386 for IgG1; r = -0.600, p = 0.142 for IgG2; r = 0.077, p = 0.227 for IgG3; r = 0.664, p = 0.051 for IgG4). However, the mean level of specific total IgG was highest in the age group of >40 years. These levels of either specific total IgG or each IgG isotype did not vary among individuals with different malaria episodes. A higher level of specific total IgG, IgG1 and IgG3 antibody response related with the lower of parasitemia density was observed although no significant correlation was found. Our data indicate that individuals exposed to vivax malaria in Thailand developed antibodies to the potential candidate vaccine antigen, PvMSP1 (C-terminal).

Pedimune in recurrent respiratory infection and diarrhoea--the Indian experience--the pride study.

OBJECTIVE: To evaluate the efficacy and tolerability of bovine colostrum in preventing recurrent episodes of upper respiratory tract infections and diarrhoea in children METHODS: 605 children (1-8 yrs) having recurrent episodes of upper respiratory tract infections or diarrhea received Bovine Colostrum (Pedimune) for 12 weeks. Total no of episodes of recurrent infections, hospitalization rate, overall well being and adverse events were assessed at every 4 weeks. RESULTS: Episodes of URTI and diarrhoea reduced significantly by 91.19 % and 86.60% at the end of therapy respectively. High to average improvement in overall well-being in 96 % of the patients were found by pediatrician while overall well-being stated by the patient/care taker was very good to good in 90.56 % of the patients. CONCLUSION: Bovine colostrum was highly effective in the prophylactic treatment of recurrent URTIs and diarrhea in reducing not only the episodes but also the hospitalization due to them.

Uso del rituximab(anticuerpo monoclonal anti-CD20) en lupus eritematoso sistémico refractario a tratamiento: Caso clínico / Rituximab (anti-CD20 monoclonal antibody) for refractory systemic lupus erythematosus: Report of one case

New therapeutic approaches that include depletion of B cells using rituximab, a chimeric monoclonal antibody directed against the B cell specific antigen CD-20 have been developed for the treatment of systemic lupus erythematosus (SLE). We report the case of a 18 years old girl with SLE that did not respond and experienced adverse effects with the use of hydroxycloroquine, methotrexate, mycophenolate mofetil, azathioprine and high-dose steroids. Rituximab was given weekly at 375 mg/m2 for four doses. The drug was well tolerated and the patient had no adverse reactions. She remains asymptomatic three months later.

Seroprevalencia de helicobacter pylori en niños de una población de la frontera colombo-venezolana / Seroprevalance of helicobacter pylori in children in a population of the colombian-venezuelan border

Con el objetivo de conocer la seroprevalencia de la infección por Helicobacter pylori (Hp) en niños de una población de la frontera colombo-venezolana, determinamos en sangre anticuerpos IgG contra Hp. Se incluyeron 98 niños, 51 por ciento del sexo masculino y 49 por ciento del sexo femenino. Encontramos IgG contra Hp en el 47 por ciento contra un 53 por ciento de muestras negativas. No hubo diferencias significativas en cuanto al sexo. La mayor frecuencia se observó en los niños de nueve años. Nuestros resultados demuestran que desde temprana edad existe una alta seroprevalencia de la infección por Hp similar a la reportada en otros países.

Efecto de la administración previa de la vacuna DPT en la respuesta de anticuerpos anti- PRP: en niños inmunizados con la vacuna PRP-T: informe preliminar / Effect of prior administration of DPT vaccine in the response of anti-PRP antibody: in children immunized with the vaccine PRP-T: preliminary report

El objetivo del estudio fue evaluar los efectos de la vacunación DPT dos semanas antes de la primera dosis de la administración de la vacuna PRP-T, sobre la respuesta de anticuerpos anti-PRP en lactantes vacunados a los 2, 4 y 6 meses de edad. Luego de la obtención del consentimiento informado escrito, 141 niños de 2 meses de edad fueron distribuidos al azar en uno de tres grupos, para ser vacunados a los 2, 4 y 6 meses de edad respectivamente. El Grupo A incluyó vacunados con DPT dos semanas previas a la primeras dosis de PRP-T; el Grupo B a aquellos vacunados con PRP-T y DPT simultáneamente, en sitios separados; y el Grupo C a los vacunados con PRP-T, dos semanas previas a la primera dosis de DPT. La segunda y la tercera dosis de ambas vacunas se administraron simultáneamente en los tres grupos. Se tomaron muestras de sangre a los 2,4, 6 y 7 meses de vida. Los sueros fueron conservados a menos de 20º centígrados hasta su envío a la Universidad de Vanderbilt, donde fueron procesados en ciego y en paralelo por el método de ELISA. Los datos serológicos fueron transformados logarítmicamente para su análisis, reportándose su antilogaritmo. Para el análisis estadístico se aplicó la prueba ANOVA, un valor p<0,05 fue considerado estadísticamente significativo. Los títulos de anticuerpos posteriores a la primera dosis en los grupos A, B y C fueron respectivamente de 6,3, 1,9 y 1,05 mcg/ml; para la segunda dosis se obtuvieron títulos de 14.6; 9,20 y 8,93 mcg/ml para cada grupo y para la tercera, los resultados fueron respectivamente de 25,68; 17,38 y 26,47 mcg/ml. El análisis de varianza demostró que después de la primera dosis el grupo A inmunizado previamente con DTP obtuvo títulos de anticuerpos significativamente más altos que los otros dos que dicha diferencia se mantuvo después de la segunda inyección, (p<0,0001 y 0,04 respectivamente) sin embargo no hubo significación estadística posterior a la aplicación de la tercera dosis (p=0,23).

Ensayo de actividad biológica de una fracción de timo: Biomodulina T / Clinical trial on the biological activity of a thymus fraction Biomodulin T

La diferenciación o maduración de linfocitos T es la acción fundamental de las hormonas del timo, por lo que utilizamos el ensayo de rosetas activas a partir de sangre de un paciente con diagnóstico de inmunodeficiencia con ataxia-telangiectasia, para determinar la actividad biológica de la biomodulina T (fracción de timo obtenida en nuestro laboratorio). Se utilizaron diferentes dosis en el ensayo y se compararon con el Levamisol. La estimulación obtenida con biomodulina T fue superior, incluso en concentración menor. Esta sustancia constituye un estimulador fisiológico de los linfocitos. Se demuestra la actividad inmunomoduladora de la biomodulina T y que la estimulación óptima se obtiene con una concentración entre 1 y 10 ug/mL aproximadamente, para este ensayo