Loading...
8 results
Search Results
Now showing 1 - 8 of 8
- The pharmacological effect of hemin in inflammatory-related diseases: protocol for a systematic reviewPublication . Estarreja, João; Caldeira, Gonçalo; Silva, Inês; Mendes, Priscila; Mateus, VanessaBackground: Hemin is a commonly used drug in the treatment of acute attacks of porphyria, due to its capability of restoring normal levels of hemoproteins and respiratory pigments. In addition, this drug has demonstrated the capacity to induce the heme oxygenase (HO) enzyme. At the moment, there are 3 known HO isoenzymes in mammals: HO-1, HO-2, and HO-3. The first of these shows cytoprotective, antioxidant, and anti-inflammatory effects. Currently, medicines used in inflammatory disorders have increased toxicity, especially over longer time frames, which highlights the need to investigate new, safer options. Indeed, the current nonclinical evidence demonstrates the potential that hemin has a significant anti-inflammatory effect in several animal models of inflammation-related diseases, such as experimental colitis, without significant side effects. However, the underlying mechanism(s) are still not fully understood. In addition, past nonclinical studies have applied different therapeutic regimens, making it relatively difficult to understand which is optimal. According to the literature, there is a lack of review articles discussing this topic, highlighting the need for a summary and analysis of the available preclinical evidence to elucidate the abovementioned issues. Therefore, a qualitative synthesis of the current evidence is essential for the research and medical communities. Objective: This systematic review aims to summarize and analyze currently available nonclinical data to ascertain the potential anti-inflammatory effect of hemin in animal models. Methods: Throughout the development of this protocol, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The comprehensive search strategy will be carried out in MEDLINE (PubMed), Web of Science, and Scopus without any filters associated with publication date. Only in vivo, nonclinical studies that evaluated the potential anti-inflammatory effect of hemin will be included. The evaluated outcomes will be the observed clinical signs, inflammatory and other biochemical markers, and macroscopic and microscopic evaluations. To analyze the potential risk of bias, we will use the risk of bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). Results: Currently, it is not possible to disclose any results since the project is still in the initial steps. More specifically, we are currently engaged in the identification of eligible articles through the application of the inclusion and exclusion criteria. The work was initiated in April 2023, and it is expected to be finished at the end of 2023. Conclusions: Concerning the major gap in the literature regarding the underlying mechanism(s) and treatment-related properties, this systematic review will be essential to clearly summarize and critically analyze the nonclinical data available, promoting a clearer vision of the potential anti-inflammatory effect of hemin.
- Novo inibidor de motor de alta especificidade em cancro gástricoPublication . Pereira, Miguel; Mendes, Priscila; Palma, João; Brito, Miguel; Ribeiro, Edna; Cervantes, Renata; Marques-Ramos, AnaO mechanistic target of rapamycin (mTOR) é uma quinase que regula o crescimento, proliferação e sobrevivência celulares. A desregulação da via de mTOR está presente em diversas patologias, sendo a sua hiperativação observada em mais de 70% de cancros humanos, incluindo cancro gástrico (CG). Apesar de existirem atualmente diversos inibidores de mTOR (mTORi), a sua utilização clínica ainda é limitada devido à elevada toxicidade associada à inibição inespecífica de outras proteínas e à inibição parcial da via. Assim, é crucial desenvolver uma nova classe de mTORi que iniba específica e totalmente a via do mTOR. As opções terapêuticas atuais em CG são invasivas e agressivas6 e sabendo que neste tipo tumoral há hiperativação da via e sobreexpressão da proteína mTOR1, uma potencial forma de restringir a progressão CG é através da utilização de um mTORi. Objetivo: Desenvolver um composto que iniba especifica e totalmente o mTOR e avaliar o seu efeito terapêutico num modelo animal de tumor gastrointestinal.
- An in vivo model of ischemic stroke to study potential pharmacological targetsPublication . Mendes, Priscila; Solas, João; Santos, Sofia; Fernandes, Adelaide; Ratilal, Bernardo; Mateus, Vanessa; Rocha, JoãoBackground: Ischemic Stroke (IS) is caused by a focal disruption in cerebral blood flow due to the occlusion of a blood vessel, most commonly the middle cerebral artery (MCA)—the ischemic cascade results in neuronal death and inflammatory response, including in situ microglia activation. Inflammation is a double‐edged sword; it can cause tissue injury but can also help in the tissue repair of the brain. The only approved pharmacological treatment for IS has strong limitations of use depending on the time post-stroke onset. Despite the efforts to develop neuroprotective agents, none have proven efficacious for the human population. Aim: The aim is to clarify the cerebral cellular behavior during the different phases of ischemia-reperfusion as it might contribute to increasing pharmacological targets toward neuroprotection. Methods: The middle cerebral artery occlusion (MCAO) in vivo model was developed (n=8). Rats were randomly divided into two groups: 1) Animals exposed to 1h of ischemia (I1h) and 2) Animals exposed to 1h of ischemia followed by 1h of reperfusion (I/R1h). Brains were collected and the expression of synaptic markers (PSD-95, Syn), inflammatory mediators (TNF-α, IL-1β, IL-10), markers of microglia (Iba1, iNOS, Arg), and astrocytes (GFAP, S100B) were determined by qRealTime-PCR and Western Blot. Results: We found decreased PSD-95 and Syn expression in the ipsilateral hemisphere of both groups (~0.5 fold-I 1h; ~0.5 fold-I/R 1h), compared to the contralateral hemisphere. Levels of IL-10 were decreased in the ipsilateral hemisphere of both groups (~0.2 fold-I 1h; ~0.4 fold-I/R 1h), compared to the contralateral hemisphere. TNF-α was higher in the I/R 1h group compared to the I 1h group. Iba1 and GFAP expression were reduced in the ipsilateral hemisphere of the I/R 1h group (~0.4 fold and 0.8 fold, respectively). Conclusions: Our results strengthen the MCAO rodent model as a potential model to study neuroinflammation as a pharmacological target. Further research is needed to clarify time-dependent changes.
- Correction: The efficacy, safety, and efficiency of the off-label use of bevacizumab in patients diagnosed with age-related macular degeneration: protocol for a systematic review and meta-analysisPublication . Estarreja, João; Mendes, Priscila; Silva, Carina; Camacho, Pedro; Mateus, Vanessa[This corrects the article DOI: 10.2196/38658.]
- The pharmacological effect of hemin in inflammatory-related diseases: a systematic reviewPublication . Estarreja, João; Caldeira, Gonçalo; Silva, Inês; Mendes, Priscila; Mateus, VanessaBackground: Hemin is clinically used in acute attacks of porphyria; however, recent evidence has also highlighted its capability to stimulate the heme oxygenase enzyme, being associated with cytoprotective, antioxidant, and anti-inflammatory effects. Indeed, current preclinical evidence emphasizes the potential anti-inflammatory role of hemin through its use in animal models of disease. Nevertheless, there is no consensus about the underlying mechanism(s) and the most optimal therapeutic regimens. Therefore, this review aims to summarize, analyze, and discuss the current preclinical evidence concerning the pharmacological effect of hemin. Methods: Following the application of the search expression and the retrieval of the articles, only nonclinical studies in vivo written in English were considered, where the potential anti-inflammatory effect of hemin was evaluated. Results: Forty-nine articles were included according to the eligibility criteria established. The results obtained show the preference of using 30 to 50 mg/kg of hemin, administered intraperitoneally, in both acute and chronic contexts. This drug demonstrates significant anti-inflammatory and antioxidant activities considering its capacity for reducing the expression of proinflammatory and oxidative markers. Conclusions: This review highlighted the significant anti-inflammatory and antioxidant effects of hemin, providing a clearer vision for the medical community about the use of this drug in several human diseases.
- Off-label use of bevacizumab in patients diagnosed with age-related macular degeneration: a systematic review and meta-analysisPublication . Estarreja, João; Mendes, Priscila; Silva, Carina; Camacho, Pedro; Mateus, VanessaBackground: Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly people. Current pharmacological treatment in vascular AMD includes anti-VEGF agents, such as ranibizumab and aflibercept. Additionally, the off-label use of bevacizumab has been shown to be effective and has a lower cost, making it an interesting pharmacological approach; however, there is no consensus about its use. Therefore, this systematic review and meta-analysis aims to evaluate the efficacy, safety, and efficiency of bevacizumab in AMD patients. Methods: This review only focused on randomized controlled clinical trials published in 2010 in the MEDLINE database that compared the effect of bevacizumab with ranibizumab. The risk of bias in each included study was assessed using the CASP Randomised Clinical Trials checklist. Results: Twelve studies were included for qualitative synthesis, and nine of them were considered for meta-analysis. Bevacizumab-treated patients showed a significantly reduced neovascularization in a longer spectrum of time; however, they had a higher incidence of endophthalmitis than those treated with ranibizumab. Regarding efficiency, the mean number of administrations was reduced in the treatment with bevacizumab in comparison to ranibizumab. Conclusions: Clinical evidence demonstrates that bevacizumab has efficacy and safety profiles comparable with ranibizumab; however, it is relatively more efficient.
- The efficacy, safety, and efficiency of the off-label use of bevacizumab in patients diagnosed with age-related macular degeneration: protocol for a systematic review and meta-analysisPublication . Estarreja, João; Mendes, Priscila; Silva, Carina; Camacho, Pedro; Mateus, VanessaBackground: Age-related macular degeneration (AMD) is recognized as the leading cause of vision loss in older people. Considering the phenomenon of aging societies worldwide, the prevalence of AMD is expected to increase gradually in the future. AMD can be divided into early, intermediate, and late stages, with the early and intermediate stages being mainly asymptomatic, and the late stage being classified as geographic atrophy, neovascular AMD, or both. Current pharmacological treatments for neovascular AMD include anti-vascular endothelial growth factors agents, such as ranibizumab, pegaptanib, and aflibercept. Additionally, it has been reported that the off-label use of intravitreally administered bevacizumab is effective. It is also lower cost than other agents, which makes it an interesting pharmacological approach. Objective: This review aims to evaluate the efficacy, safety, and efficiency of bevacizumab for the treatment of neovascular AMD. Methods: This review will only consider randomized controlled clinical trials that compare the use of bevacizumab with another pharmacological agent or placebo in patients aged 50 years and older who are diagnosed with vascular AMD. It will exclude studies that include participants diagnosed with polypoidal choroidal vasculopathy or retinal angiomatous proliferation. To identify and select relevant articles, we will develop a highly sensitive search strategy and apply it in MEDLINE via the PubMed platform. Upon selection of the studies and analysis of the titles, abstracts, and full texts, the results will be presented according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis and extraction of the data will be performed by 2 independent reviewers. The risk of bias will be evaluated with the Critical Appraisal Skills Programme (CASP) checklist. Finally, the same reviewers will also perform a quality assessment of the included studies with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Results: The search strategy, after the application of the inclusion and exclusion criteria, identified 15 randomized clinical trials, which are currently being analyzed. This project has no funding and it has been developed by a multidisciplinary research team of pharmacologists and orthoptists. The study was initiated in May 2021 and it is expected to conclude by the end of 2023. Conclusions: This review will provide a synthesis of current information and underlying evidence about the off-label use of bevacizumab in neovascular AMD. It will provide a clearer vision of a possible new pharmacological approach, as well as the most suitable treatment designs, for the treatment of neovascular AMD.
- Effect of carbamylated erythropoietin in a chronic model of TNBS-induced colitisPublication . Silva, Inês; Gomes, Mário; Alípio, Carolina; Vitoriano, Jéssica; Estarreja, João; Mendes, Priscila; Pinto, Rui; Mateus, VanessaBackground: Inflammatory bowel disease (IBD) is a public health issue with a growing prevalence, which can be divided into two phenotypes, namely Crohn's disease (CD) and ulcerative colitis (UC). Currently, used therapy is based only on symptomatic and/or palliative pharmacological approaches. These treatments seek to induce and maintain remission of the disease and ameliorate its secondary effects; however, they do not modify or reverse the underlying pathogenic mechanism. Therefore, it is essential to investigate new potential treatments. Carbamylated erythropoietin (cEPO) results from the modification of the Erythropoietin (EPO) molecule, reducing cardiovascular-related side effects from the natural erythropoiesis stimulation. cEPO has been studied throughout several animal models, which demonstrated an anti-inflammatory effect by decreasing the production of several pro-inflammatory cytokines. Aim: This study aimed to evaluate the efficacy and safety of cEPO in a chronic TNBS-induced colitis model in rodents. Methods: Experimental colitis was induced by weekly intrarectal (IR) administrations of 1% TNBS for 5 weeks in female CD-1 mice. Then, the mice were treated with 500 IU/kg/day or 1000 IU/kg/day of cEPO through intraperitoneal injections for 14 days. Results: cEPO significantly reduced the concentration of alkaline phosphatase (ALP), fecal hemoglobin, tumor necrosis factor (TNF)-α, and interleukin (IL)-10. Also, it demonstrated a beneficial influence on the extra-intestinal manifestations, with the absence of significant side effects of its use. Conclusion: Considering the positive results from cEPO in this experiment, it may arise as a new possible pharmacological approach for the future management of IBD.