The Pharmacological Effect of Hemin in Inflammatory-Related Diseases: A Systematic Review.

BACKGROUND: 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.

Blood count, endocrine, immunologic, renal, and hepatic markers in a case-control animal study of induced periodontitis in female rodents.

Introduction: Periodontitis is a non-communicable chronic inflammatory disease with a systemic burden. Animal models of induced periodontitis help elucidate the mechanisms by which periodontal inflammation drives systemic effects. Studying this systemic involvement over longer follow-up periods may provide a strong foundation for future research on the association between diseases and periodontitis, particularly in female rats. Therefore, we aimed to compare blood, endocrine, immunologic, renal, and hepatic markers in a rat model of induced periodontitis in females with their control counterparts. Methods: Experimental periodontitis was induced in 20 female Wistar rats by the application and maintenance of silk ligatures on the upper molars. The rats were then assessed for macroscopical analysis, complete blood count, and biochemical, endocrine, and immunologic markers at 21, 28, 42, and 56 days. Results: Chronic periodontal inflammation was observed after 42 days of exposure to the ligatures. Additionally, it was also possible to notice significant systemic manifestations, such as the reduction of triiodothyronine and thyroxine levels, along with an increase in the expression of alkaline phosphatase, gamma-glutamyl transpeptidase, and lactate dehydrogenase. Discussion: The study's findings imply that certain changes can be underscored to highlight a reduced risk of conception. Notably, previous investigations have indicated that subfertile women exhibit lower levels of thyroid hormones and elevated lactate dehydrogenase expression. Despite the absence of preclinical data delineating a possible association between periodontitis and female infertility, the results of this study may prove to be a crucial contribution to both the scientific and medical fields.

The Pharmacological Effect of Hemin in Inflammatory-Related Diseases: Protocol for a Systematic Review.

BACKGROUND: 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 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. TRIAL REGISTRATION: PROSPERO CRD42023406160; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=406160. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48368.

Effect of Carbamylated Erythropoietin in a Chronic Model of TNBS-Induced Colitis.

BACKGROUND: 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.

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-Analysis.

[This corrects the article DOI: 10.2196/38658.].

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-Analysis.

BACKGROUND: 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 factor 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 a 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. 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. TRIAL REGISTRATION: PROSPERO CRD42021244931; https://tinyurl.com/p6m5ycpk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38658.

Gut microbiota profile of COVID-19 patients: Prognosis and risk stratification (MicroCOVID-19 study).

Background: Gut microbiota is intrinsically associated with the immune system and can promote or suppress infectious diseases, especially viral infections. This study aims to characterize and compare the microbiota profile of infected patients with SARS-CoV-2 (milder or severe symptoms), non-infected people, and recovered patients. This is a national, transversal, observational, multicenter, and case-control study that analyzed the microbiota of COVID-19 patients with mild or severe symptoms at home, at the hospital, or in the intensive care unit, patients already recovered, and healthy volunteers cohabiting with COVID-19 patients. DNA was isolated from stool samples and sequenced in a NGS platform. A demographic questionnaire was also applied. Statistical analysis was performed in SPSS. Results: Firmicutes/Bacteroidetes ratios were found to be significantly lower in infected patients (1.61 and 2.57) compared to healthy volunteers (3.23) and recovered patients (3.89). Furthermore, the microbiota composition differed significantly between healthy volunteers, mild and severe COVID-19 patients, and recovered patients. Furthermore, Escherichia coli, Actinomyces naeslundii, and Dorea longicatena were shown to be more frequent in severe cases. The most common COVID-19 symptoms were linked to certain microbiome groups. Conclusion: We can conclude that microbiota composition is significantly affected by SARS-CoV-2 infection and may be used to predict COVID-19 clinical evolution. Therefore, it will be possible to better allocate healthcare resources and better tackle future pandemics.

Efficacy and safety of erythropoietin in a chronic model of Inflammatory Bowel Disease.

BACKGROUND: Inflammatory Bowel Disease (IBD) is recognized as a group of chronic inflammatory disorders, localized in the gastrointestinal tract, which does not have a cure known. Indeed, the pharmacological approaches, commonly used, demonstrate significant toxicity, which highlights the need of investigating new possible treatments. Erythropoietin (EPO) is clinically used in anemic patients, with chronic renal insufficiency, due to its erythropoietic effect. However, it has also been described other non-erythropoietic effects, such as an anti-inflammatory role. There is already preclinical evidence about its anti-inflammatory effect in the IBD context, namely in an acute model of colitis in mice. Therefore, it is relevant to ascertain its anti-inflammatory effect in a chronic model, but mainly its hematopoietic side effect, during chronic treatment. AIM: This experiment aims to evaluate the efficacy and safety of EPO treatment in a chronic 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rodents. METHODS: The induction of chronic colitis consistedofn five weekly intrarectal administrations of 1% TNBS, and then mice were treated daily with 500 IU/Kg or 1000 IU/Kg of EPO, through intraperitoneal injections, for 14 days. RESULTS: EPO demonstrated a significant anti-inflammatory effect, translated by a significant reduction of the concentration oftumorr necrosis factor-α, fecal calprotectin, and fecal hemoglobin. Moreover, it has also been demonstrated to be safe, considering the cardiovascular system, in terms of extraintestinal manifestations, namely at renal and hepatic functions. CONCLUSIONS: EPO demonstrated to be a promising pharmacological approach to be considered in the management of IBD, being an interesting target for drug repositioning.

Hemin Ameliorates the Inflammatory Activity in the Inflammatory Bowel Disease: A Non-Clinical Study in Rodents.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Currently, there is no cure, and pharmacological treatment aims to induce and maintain remission in patients, so it is essential to investigate new possible treatments. Hemin is a heme-oxygenase inducer which can confer anti-inflammatory, cytoprotective, and antiapoptotic effects; therefore, it can be considered an asset for different gastrointestinal pathologies, namely for IBD. AIM: This experiment aims to evaluate the efficacy and safety of hemin, in a chronic 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rodents. METHODS: The induction of chronic colitis consisted of five weekly intrarectal administrations of 1% TNBS. Then, the mice were treated daily with 5 mg/kg/day or 10 mg/kg/day of hemin, through intraperitoneal injections, for 14 days. RESULTS: Hemin demonstrated an anti-inflammatory effect through the reduction in tumor necrosis factor (TNF)-α levels, fecal calprotectin, and fecal hemoglobin. It was also found to be safe in terms of extraintestinal manifestations, since hemin did not promote renal and/or hepatic changes. CONCLUSIONS: Hemin could become an interesting tool for new possible pharmacological approaches in the management of IBD.

Anti-Inflammatory Effect of Topiramate in a Chronic Model of TNBS-Induced Colitis.

Inflammatory bowel disease (IBD) is characterized by a chronic and relapsing inflammatory response in the gastrointestinal tract, resulting in severe symptoms such as abdominal pain, vomiting, diarrhea, bloody stools, and weight loss. Currently, there is no cure, and the pharmacological treatment includes drugs that induce and keep the patient in remission, not reversing the underlying pathogenic mechanism. These therapies, in the long term, may cause various side effects and complications, which has increased the need to investigate new, more effective, and safer pharmacological approaches. In preclinical studies, topiramate has demonstrated a potential anti-inflammatory effect by inhibiting the production of several pro-inflammatory cytokines. This study aimed to investigate the effect of topiramate in a chronic TNBS-induced colitis model in rodents. Experimental colitis was induced by four intrarectal administrations of 1% TNBS in female CD-1 mice. Topiramate 10 and 20 mg were administered intraperitoneally for 14 days. Several parameters were evaluated, such as bodyweight, alkaline phosphatase (ALP), fecal hemoglobin, fecal calprotectin, tumor necrosis factor (TNF)-α, and interleukin (IL)-10. Topiramate reduces TNBS-induced colonic damage in a model of chronic experimental colitis and normalizes the stool consistency and anus appearance. Additionally, topiramate significantly reduced the concentration of ALP, fecal hemoglobin, fecal calprotectin, TNF-α, and IL-10, demonstrating it to be a promising pharmacological approach for the treatment of IBD in the future.

Effect of Aqueous Extract of Phenolic Compounds Obtained from Red Wine in Experimental Model of Colitis in Mice.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder represented by Crohn's disease and ulcerative colitis. Currently, there is no cure and pharmacological treatment aims to induce and maintain remission on patients. Because the therapy reveals a relatively high toxicity, during a long-term utilization, it is essential to investigate new pharmacological approaches. Polyphenols, commonly present on red wine, have shown health-beneficial effects related to their antioxidant and anti-inflammatory effects through the inhibition of NF-kB activation, COX-2 and iNOS induction. In this sense, it would be interesting to study their effects in an IBD context. Therefore, this study aims to evaluate the effects of an aqueous extract of phenolic compounds in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced model of colitis. METHOD: Experimental colitis was induced in mice through an intrarectal administration of TNBS and then the mice were treated with an aqueous extract of phenolic compounds intraperitoneally for four days. RESULTS AND DISCUSSION: The extract demonstrated an anti-inflammatory effect, reducing TNF-α levels in the colon, and had a beneficial effect on the extraintestinal manifestations related to IBD, without any significant side effects. The extract of phenolic compounds demonstrated to be a valuable object of study for the management of IBD in the future.

Chemically Induced Colitis-Associated Cancer Models in Rodents for Pharmacological Modulation: A Systematic Review.

Animal models for colitis-associated colorectal cancer (CACC) represent an important tool to explore the mechanistic basis of cancer-related inflammation, providing important evidence that several inflammatory mediators play specific roles in the initiation and perpetuation of colitis and CACC. Although several original articles have been published describing the CACC model in rodents, there is no consensus about the induction method. This review aims to identify, summarize, compare, and discuss the chemical methods for the induction of CACC through the PRISMA methodology. METHODS: We searched MEDLINE via the Pubmed platform for studies published through March 2021, using a highly sensitive search expression. The inclusion criteria were only original articles, articles where a chemically-induced animal model of CACC is described, preclinical studies in vivo with rodents, and articles published in English. RESULTS: Chemically inducible models typically begin with the administration of a carcinogenic compound (as azoxymethane (AOM) or 1,2-dimethylhydrazine (DMH)), and inflammation is caused by repeated cycles of colitis-inducing agents (such as 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sulfate sodium (DSS)). The strains mostly used are C57BL/6 and Balb/c with 5-6 weeks. To characterize the preclinical model, the parameters more used include body weight, stool consistency and morbidity, inflammatory biomarkers such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß, angiogenesis markers such as proliferating cell nuclear antigen (PCNA), marker of proliferation Ki-67, and caspase 3, the presence of ulcers, thickness or hyperemia in the colon, and histological evaluation of inflammation. CONCLUSION: The AOM administration seems to be important to the CACC induction method, since the carcinogenic effect is achieved with just one administration. DSS has been the more used inflammatory agent; however, the TNBS contribution should be more studied, since it allows a reliable, robust, and a highly reproducible animal model of intestinal inflammation.

Chronic Experimental Model of TNBS-Induced Colitis to Study Inflammatory Bowel Disease.

Background: Inflammatory bowel disease (IBD) is a world healthcare problem. In order to evaluate the effect of new pharmacological approaches for IBD, we aim to develop and validate chronic trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Methods: Experimental colitis was induced by the rectal administration of multiple doses of TNBS in female CD-1 mice. The protocol was performed with six experimental groups, depending on the TNBS administration frequency, and two control groups (sham and ethanol groups). Results: The survival rate was 73.3% in the first three weeks and, from week 4 until the end of the experimental protocol, the mice's survival remained unaltered at 70.9%. Fecal hemoglobin presented a progressive increase until week 4 (5.8 ± 0.3 µmol Hg/g feces, p < 0.0001) compared with the ethanol group, with no statistical differences to week 6. The highest level of tumor necrosis factor-α was observed on week 3; however, after week 4, a slight decrease in tumor necrosis factor-α concentration was verified, and the level was maintained until week 6 (71.3 ± 3.3 pg/mL and 72.7 ± 3.6 pg/mL, respectively). Conclusions: These findings allowed the verification of a stable pattern of clinical and inflammation signs after week 4, suggesting that the chronic model of TNBS-induced colitis develops in 4 weeks.

Potential Anti-Inflammatory Effect of Rosmarinus officinalis in Preclinical In Vivo Models of Inflammation.

This systematic review aimed to evaluate the potential anti-inflammatory effect of Rosmarinus officinalis in preclinical in vivo models of inflammation. A search was conducted in the databases PubMed, Scopus, and Web of Science, with related keywords. The inclusion criteria were inflammation, plant, and studies on rats or mice; while, the exclusion criteria were reviews, studies with in vitro models, and associated plants. The predominant animal models were paw edema, acute liver injury, and asthma. Rosemary was more commonly used in its entirety than in compounds, and the prevalent methods of extraction were maceration and hydrodistillation. The most common routes of administration reported were gavage, intraperitoneal, and oral, on a route-dependent dosage. Treatment took place daily, or was single-dose, on average for 21 days, and it more often started before the induction. The most evaluated biomarkers were tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-10, myeloperoxidase (MPO), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and superoxide dismutase (SOD). The best results emerged at a dose of 60 mg/kg, via IP of carnosic acid, a dose of 400 mg/kg via gavage of Rosmarinus officinalis, and a dose of 10 mg/kg via IP of rosmarinic acid. Rosmarinus officinalis L. showed anti-inflammatory activity before and after induction of treatments.

Potential anti-inflammatory effect of erythropoietin in non-clinical studies in vivo: A systematic review.

Erythropoietin (EPO) is a hypoxia-induced hormone produced in adult kidneys with erythropoietic and non-erythropoietic effects. In vivo studies represent an important role to comprehend the efficacy and safety in the early phase of repurposing drugs. The aim is to evaluate the potential anti-inflammatory effect of EPO observed in animal models of disease. Following PRISMA statements, electronic database Medline via PubMed platform was used to search articles with the research expression ((erythropoietin [MeSH Terms]) AND (inflammation [MeSH Terms]) AND (disease models, animal [MeSH Terms])). The inclusion criteria were original articles, studies where EPO was administered, studies where inflammation was studied and/or evaluated, non-clinical studies in vivo with rodents, and articles published in English. Thirty-six articles met the criteria for qualitative analysis. Exogenous EPO was used in models of sepsis, traumatic brain injury, and autoimmune neuritis, with an average of 3000 IU/Kg for single and multiple doses, using mice and rats. Biomarkers such as immune-related effectors, cytokines, reactive oxygen species, prostaglandins, and other biomarkers were assessed. EPO has been recognized as a multifunctional cytokine with anti-inflammatory properties, showing its significant effect both in acute and chronic models of inflammation. Further non-clinical studies are suggested for the enlightenment of anti-inflammatory mechanisms of EPO in lower doses, allowing us to understand the translational data for humans.

Stop! Graphic Health Warnings Enhance Inhibitory Control in Adolescents: An Event-Related Potential Study.

INTRODUCTION: The majority of smokers begin consumption in adolescence and the earlier initiation of cigarette smoking is associated with a greater likelihood of cigarette dependence. Graphic health warnings (GHW) are one of the most used strategies to communicate the consequences of cigarette smoking, but little is known about their ability to increase inhibitory control and thus prevent consumption. The objective of the present study was to evaluate the effects of different sizes of GHWs on inhibitory control in adolescents. We hypothesized that GHWs promote inhibitory control, and increasing GHW size, enhance inhibitory control. METHODS: Fifty-nine participants completed a Go/No-Go task during electroencephalographic recording. The No-Go stimuli were pictures of cigarette packs without GHWs, and cigarette packs with GHWs that covered 30% or 60% of the front (main side) of the pack. The event-related potential N200 component and behavioral measures in the Go/No-Go task were analyzed. RESULTS: Separate mixed-model analysis of variance (ANOVAs) were used for N200 component (amplitude and latency) and behavioral data. The GHWs increased the amplitude of the N200 potential, especially GHWs that covered 60% of the front of the pack. The behavioral data showed that GHWs that covered 60% of the front of the pack generated higher a percentage of accuracy in No-Go trials (ie, fewer commission errors). CONCLUSIONS: These results suggest that GHWs increase inhibitory control in adolescents, especially when the GHWs cover 60% of the front of the cigarette pack. IMPLICATIONS: GHWs with an increased size (60% of the front of the cigarette pack vs. 30%, the minimum size, proposed by the World Health Organization) recruit additional cognitive resources and thus can effectively increase inhibitory control both in adolescent smokers and nonsmokers. Accordingly, the use of larger GHW has the potential of becoming an effective public policy strategy to inhibit smoking in adolescents.

Preclinical Study in Vivo for New Pharmacological Approaches in Inflammatory Bowel Disease: A Systematic Review of Chronic Model of TNBS-Induced Colitis.

The preclinical studies in vivo provide means of characterizing physiologic interactions when our understanding of such processes is insufficient to allow replacement with in vitro systems and play a pivotal role in the development of a novel therapeutic drug cure. Chemically induced colitis models are relatively easy and rapid to develop. The 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis model is one of the main models in the experimental studies of inflammatory bowel disease (IBD) since inflammation induced by TNBS mimics several features of Crohn's disease. This review aims to summarize the existing literature and discuss different protocols for the induction of chronic model of TNBS-induced colitis. We searched MEDLINE via Pubmed platform for studies published through December 2018, using MeSH terms (Crohn Disease.kw) OR (Inflammatory Bowel Diseases.kw) OR (Colitis, Ulcerative.kw) AND (trinitrobenzenesulfonic acid.kw) AND (disease models, animal.kw) AND (mice.all). The inclusion criteria were original articles, preclinical studies in vivo using mice, chronic model of colitis, and TNBS as the inducer of colitis and articles published in English. Chronic TNBS-induced colitis is made with multiple TNBS intrarectal administrations in an average dose of 1.2 mg using a volume lower than 150 µL in 50% ethanol. The strains mostly used are Balb/c and C57BL/6 with 5-6 weeks. To characterize the preclinical model the parameters more used include body weight, stool consistency and morbidity, inflammatory biomarkers like interferon (IFN)-γ, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10, presence of ulcers, thickness or hyperemia in the colon, and histological evaluation of the inflammation. Experimental chronic colitis is induced by multiple rectal instillations of TNBS increasing doses in ethanol using Balb/c and C57BL/6 mice.

Reduction of Inflammation and Colon Injury by a Spearmint Phenolic Extract in Experimental Bowel Disease in Mice.

Background: Inflammatory Bowel Diseases (IBD) encompasses both Crohn's Disease and Ulcerative Colitis, known to be connected to an enlarged risk for developing colorectal cancer (CRC). Spearmint (Mentha spicata L.) is a Mediterranean plant used as an aromatic agent, and studies have mainly focused on the essential oil suggesting an anti-inflammatory activity. This work aimed to perform a preliminary screening of the in vivo anti-inflammatory effects of a spearmint phenolic extract in an acute inflammation model, in a chronic inflammation model of colitis, and also study the effects in vitro on a colon cancer model. Methods: Spearmint extract was administered to rats of a paw oedema model (induced by carrageenan) and to mice from a TNBS-induced colitis model in parallel with studies using HT-29 CRC cells. Results: Administration of the extract led to reduced paw inflammation, reduction of colon injury and inflammation, with attenuation of histological markers, and reduction of iNOS expression. It repressed the in vitro movement of HT-29 cells in a wound healing assay. Conclusions: These findings suggest that spearmint extract exhibits acute and chronic anti-inflammatory activity and is able to inhibit migration of cancer cells, suggesting a potential role in the supplementary therapy of IBD patients.

Hemin reduces inflammation associated with TNBS-induced colitis.

PURPOSE: Hemin is a heme-oxygenase inducer, which can confer anti-inflammatory, cytoprotective, and antiapoptotic effects. These properties are beneficial therapeutical effects to inflammatory bowel disease (IBD). IBD is a worldwide health problem characterized by chronic inflammation of intestinal epithelium, which promotes intestinal and extraintestinal symptomatology. Current treatment only induces and maintains the patient in remission and results in many side effects. The research of other pharmacologic approaches is crucial to the treatment of IBD. The aim of this study is to evaluate the effect of hemin in the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. MATERIALS AND METHODS: Male CD-1 mice with TNBS-induced colitis were treated with a daily dose of hemin 5 mg/kg body weight/day and 10 mg/kg body weight/day intraperitoneal, during 4 days. The evaluated parameters were fecal hemoglobin, alkaline phosphatase (ALP), myeloperoxidase, tumor necrosis factor-α, interleukin (IL)-1ß, IL-10, histopathologic analysis, urea, creatinine, and alanine aminotransferase. RESULTS: The hemin-treated mice presented a decrease in fecal hemoglobin, ALP, and proinflammatory cytokine concentrations compared to the TNBS group. Histopathology analysis confirmed the decrease in lesion extension produced by hemin. CONCLUSION: These findings suggest that hemin treatment reduces hemorrhagic focus, intestinal damage, tissue inflammation, and lesion extension associated with experimental colitis.

Actitudes hacia la labor profesional del psicólogo en Bogotá: un estudio descriptivo comparativo según el tiempo en terapia / Attitudes toward the psychologist professional work in Bogotá: a descriptive comparative study according to therapy time

Resumen La presente investigación tuvo como objetivo determinar la actitud hacia la labor profesional del psicólogo en una muestra bogotana, según los tiempos de permanencia en terapia psicológica. Para ello se llevó a cabo un estudio de tipo descriptivo con método de comparación de grupos. Se aplicó la escala de "actitudes" frente a la labor profesional del psicólogo a una muestra de 540 personas de nacionalidad colombiana, residentes en Bogotá. Se encontró una actitud neutra hacia la labor profesional del psicólogo, destacando una mejor actitud por parte de las mujeres en comparación con los hombres, asimismo, una actitud más favorable en los participantes que han asistido mayor tiempo a terapia psicológica, actitud que empeora tras los 6 meses.

Abstract The objective of this investigation was to determine the attitude toward the psychologist professional work in a Bogotá sample, according to the psychological therapy's time. It has been made a descriptive study with a group comparative method, and the ¼Attitude toward the Psychologist Professional Work" was used in a scale to a Bogotá sample of 540 people. A neutral attitude was founded, toward the psychologist professional work, highlihting a better attitude of women in comparation with men's attitude. Nevertheless the most favorable attitude of the sample was from people who received psychological therapy for more time, attitude that gets worse after 6 months.