RESUMO

Objective: Throughout microsurgical anastomosis, many surgeons use topical vasodilators in order to reduce pathological vasospasm. It was carried out an experimental study comparing the effectiveness of topical use of Nitroglycerin, Papaverine, Magnesium sulfate over a control group in the femoral artery and vein of rats, in reducing prolonged vasospasm. Methods: Randomized comparative experimental study in 15 rats, divided into four groups. The external diameter of the vases soaked in the randomized solution was measured. For statistical analysis, it was calculated the percentual increase in the external diameter of the vessels. Results: A statistically significant increase in arterial dilation was observed after 10 minutes of topical application of 10% magnesium sulfate compared to the control group, with p = 0.044 . No other drug showed a vasodilator effect superior to the control group. Magnesium sulfate at 10% is still not used in microsurgery and costs 15 times less than papaverine, the standard drug for topical vasodilation in clinical cases at our service. Conclusion: Magnesium sulfate had better vasodilating effects over the control group after 10 minutes of arterial microanastomosis. None of the tested drugs have presented superior vasodilating effects over each other nor the control group after venous microanastomosis. Level of evidence II, Experimental study, Randomized Trial.

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Objetivo: Durante a anastomose microcirúrgica, muitos cirurgiões utilizam vasodilatadores tópicos para reduzir o vasoespasmo prolongado patológico, assim reduzindo o risco de complicações vasculares. Entretanto, ainda faltam dados experimentais para identificação da droga padrão-ouro para vasodilatadores tópicos em microcirurgia e sua avaliação de análise de custo, já que a droga geralmente utilizada para este objetivo é baseada, na maior parte dos casos, na experiência do cirurgião. Métodos: Foi realizado um estudo experimental comparativo randomizado, avaliando a eficácia do uso tópico de Nitroglicerina, Papaverina e Sulfato de Magnésio em relação a um grupo controle, na redução do vasoespasmo na artéria e veia femoral de ratos. Foram avaliados o diâmetro externo dos vasos embebidos em solução randomizada dos fármacos para vasodilatação. Após cálculo do aumento percentual no diâmetro externo dos vasos, foi realizada análise estatística. Resultados: Observou-se aumento estatisticamente significativo da dilatação arterial após 10 minutos de aplicação tópica de sulfato de magnésio a 10% em relação ao grupo controle, com p = 0,044. Nenhuma outra droga apresentou efeito vasodilatador superior ao grupo controle. O sulfato de magnésio a 10% ainda não é utilizado em microcirurgia e apresenta custo até 15 vezes menor quando comparado com a papaverina, droga padrão para vasodilatação tópica em casos clínicos em nosso serviço. Conclusão: O sulfato de magnésio apresentou melhor efeito vasodilatador quando comparado ao grupo controle, após 10 minutos da microanastomose arterial. Nenhum dos fármacos testados apresentou efeito vasodilatador superior após a microanastomose venosa. Nível de Evidência II, Estudo experimental, Ensaio Randomizado.

RESUMO

The human malaria-Aotus monkey model has served the malaria research community since its inception in 1966 at the Gorgas Memorial Laboratory (GML) in Panama. Spanning over five decades, this model has been instrumental in evaluating the in vivo efficacy and pharmacokinetics of a wide array of candidate antimalarial drugs, whether used singly or in combination. The animal model could be infected with drug-resistant and susceptible Plasmodium falciparum and Plasmodium vivax strains that follow a characteristic and reproducible course of infection, remarkably like human untreated and treated infections. Over the years, the model has enabled the evaluation of several synthetic and semisynthetic endoperoxides, for instance, artelinic acid, artesunate, artemether, arteether, and artemisone. These compounds have been evaluated alone and in combination with long-acting partner drugs, commonly referred to as artemisinin-based combination therapies, which are recommended as first-line treatment against uncomplicated malaria. Further, the model has also supported the evaluation of the primaquine analog tafenoquine against blood stages of P. vivax, contributing to its progression to clinical trials and eventual approval. Besides, the P. falciparum/Aotus model at GML has also played a pivotal role in exploring the biology, immunology, and pathogenesis of malaria and in the characterization of drug-resistant P. falciparum and P. vivax strains. This minireview offers a historical overview of the most significant contributions made by the Panamanian owl monkey (Aotus lemurinus lemurinus) to malaria chemotherapy research.

Assuntos

Antimaláricos , Artemisininas , Modelos Animais de Doenças , Animais , Antimaláricos/uso terapêutico , Antimaláricos/farmacocinética , Antimaláricos/farmacologia , Artemisininas/uso terapêutico , Artemisininas/farmacologia , Humanos , Panamá , Aotidae , Plasmodium falciparum/efeitos dos fármacos , Malária/tratamento farmacológico , Plasmodium vivax/efeitos dos fármacos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Artesunato/uso terapêutico , Artesunato/farmacologia , Artesunato/farmacocinética , Malária Vivax/tratamento farmacológico , Malária Vivax/parasitologia , História do Século XX , Aminoquinolinas

RESUMO

Given that Agaricus bisporus, an edible mushroom, has demonstrated antioxidant properties, our investigation aimed to assess whether Agaricus bisporus could mitigate the toxic effects of lead (Pb) on Caenorhabditis elegans (C. elegans) model. A dose-response study was conducted involving Pb and Agaricus bisporus to determine appropriate doses. Subsequently, a co-exposure study utilizing C. elegans strains N2 and CL2166 was implemented, with groups designated as Control, Pb, Agaricus bisporus, and Pb + Agaricus bisporus. Our findings revealed that co-exposure to Pb + 100 mg/mL Agaricus bisporus resulted in reduced embryonic and larval lethality, increased brood size, and enhanced motility compared to nematodes exposed solely to Pb. Notably, our observations indicated a transfer of reproductive toxicity from nematode parents to their offspring. Thus, Agaricus bisporus may play a significant role in Pb detoxification, suggesting its potential as a natural antioxidant for neutralizing the detrimental effects of Pb on reproductive health.

Assuntos

Agaricus , Caenorhabditis elegans , Chumbo , Reprodução , Animais , Caenorhabditis elegans/efeitos dos fármacos , Chumbo/toxicidade , Reprodução/efeitos dos fármacos , Antioxidantes/farmacologia , Larva/efeitos dos fármacos

RESUMO

BACKGROUND: Infections are complications in the wound healing process, and their treatment can lead to antibiotic overuse and bacterial resistance. Antimicrobial photodynamic therapy (aPDT) is used to treat infectious diseases caused by fungi, viruses, or bacteria. Methylene blue (MB) and its derivatives are commonly used dyes in antimicrobial photodynamic therapy (aPDT-MB). METHODS: This study is a PRISMA systematic review of animal models used to discuss the usefulness and therapeutic parameters of aPDT-MB or its derivatives for treating infected skin wounds. RESULTS: After an extensive literature review, 13 controlled trials totaling 261 animals were selected to evaluate skin infection by leishmaniasis and cutaneous bacterial and fungal infections. All studies found results favoring the use of aPDT-MB. Great variability in parameters was found for radiant exposure from 12 to 360 J/cm2, MB diluted in saline solution or distilled water, irradiation time from 40 to 3600 s, irradiance most commonly at a maximum of 100 mW/cm2, and wavelength used mainly in the 630-670 nm range. CONCLUSION: MB is a safe and promising agent used as a photosensitizer in aPDT for skin-infected lesions. There is great variability in the parameters found. Comparisons concerning concentration, irradiation time, and light intensity need to be performed.

Assuntos

Azul de Metileno , Fotoquimioterapia , Fármacos Fotossensibilizantes , Animais , Modelos Animais de Doenças , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico

RESUMO

The irreproducibility in scientific research has become a critical issue. Despite the essential role of rigorous methodology in constructing a scientific article, more than half of publications, on average, are considered non-reproducible. The implications of this irreproducibility extend to reliability problems, hindering progress in technological production and resulting in substantial financial losses. In the context of laboratory animal research, this work emphasizes the importance of choosing an appropriate experimental model within the 3R's principle (Refine, Reduce, Replace). This study specifically addresses a deficiency in data specification in scientific articles, revealing inadequacies in the description of crucial details, such as environmental conditions, diet, and experimental procedures. For this purpose, 124 articles from journals with relevant impact factors were analyzed, conducting a survey of data considered important for the reproducibility of studies. Important flaws in the presentation of data were identified in most of the articles evaluated. The results of this study highlight the need to improve the description of essential information, standardizing studies, and ensuring the reproducibility of experiments in areas such as metabolism, immunity, hormones, stress, among others, to enhance the reliability and reproduction of experimental results, aligning with international guidelines such as ARRIVE and PREPARE.

RESUMO

Sterol 14-demethylase (CYP51) inhibitors, encompassing new chemical entities and repurposed drugs, have emerged as promising candidates for Chagas disease treatment, based on preclinical studies reporting anti-Trypanosoma cruzi activity. Triazoles like ravuconazole (RAV) and posaconazole (POS) progressed to clinical trials. Unexpectedly, their efficacy was transient in chronic Chagas disease patients, and their activity was not superior to benznidazole (BZ) treatment. This paper aims to summarize evidence on the global activity of CYP51 inhibitors against T. cruzi by applying systematic review strategies, risk of bias assessment, and meta-analysis from in vivo studies. PubMed and Embase databases were searched for original articles, obtaining fifty-six relevant papers meeting inclusion criteria. Characteristics of animal models, parasite strain, treatment schemes, and cure rates were extracted. Primary outcomes such as maximum parasitaemia values, survival, and parasitological cure were recorded for meta-analysis, when possible. The risk of bias was uncertain in most studies. Animals treated with itraconazole, RAV, or POS survived significantly longer than the infected non-treated groups (RR = 4.85 [3.62, 6.49], P < 0.00001), and they showed no differences with animals treated with positive control drugs (RR = 1.01 [0.98, 1.04], P = 0.54). Furthermore, the overall analysis showed that RAV or POS was not likely to achieve parasitological cure when compared with BZ or NFX treatment (OD = 0.49 [0.31, 0.77], P = 0.002). This systematic review contributes to understanding why the azoles had failed in clinical trials and, more importantly, how to improve the animal models of T. cruzi infection by filling the gaps between basic, translational, and clinical research.

Assuntos

Inibidores de 14-alfa Desmetilase , Doença de Chagas , Modelos Animais de Doenças , Trypanosoma cruzi , Animais , Humanos , Inibidores de 14-alfa Desmetilase/farmacologia , Inibidores de 14-alfa Desmetilase/uso terapêutico , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Esterol 14-Desmetilase/metabolismo , Tiazóis , Resultado do Tratamento , Triazóis/uso terapêutico , Triazóis/farmacologia , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos

RESUMO

Alterations in cognitive and non-cognitive cerebral functions characterize Alzheimer's disease (AD). Cortical and hippocampal impairments related to extracellular accumulation of Aß in AD animal models have been extensively investigated. However, recent reports have also implicated intracellular Aß in limbic regions, such as the nucleus accumbens (nAc). Accumbal neurons express high levels of inhibitory glycine receptors (GlyRs) that are allosterically modulated by ethanol and have a role in controlling its intake. In the present study, we investigated how GlyRs in the 2xTg mice (AD model) affect nAc functions and ethanol intake behavior. Using transgenic and control aged-matched litter mates, we found that the GlyRα2 subunit was significantly decreased in AD mice (6-month-old). We also examined intracellular calcium dynamics using the fluorescent calcium protein reporter GCaMP in slice photometry. We also found that the calcium signal mediated by GlyRs, but not GABAAR, was also reduced in AD neurons. Additionally, ethanol potentiation was significantly decreased in accumbal neurons in the AD mice. Finally, we performed drinking in the dark (DID) experiments and found that 2xTg mice consumed less ethanol on the last day of DID, in agreement with a lower blood ethanol concentration. 2xTg mice also showed lower sucrose consumption, indicating that overall food reward was altered. In conclusion, the data support the role of GlyRs in nAc neuron excitability and a decreased glycinergic activity in the 2xTg mice that might lead to impairment in reward processing at an early stage of the disease.

Assuntos

Doença de Alzheimer , Núcleo Accumbens , Receptores de Glicina , Camundongos , Doença de Alzheimer/metabolismo , Núcleo Accumbens/metabolismo , Receptores de Glicina/metabolismo , Camundongos Endogâmicos C57BL , Etanol , Camundongos Transgênicos , Cálcio/metabolismo , Recompensa , Sacarose/metabolismo , Atividade Motora , Ansiedade , Neurônios/metabolismo

RESUMO

Klebsiella pneumoniae is among the most relevant pathogens worldwide, causing high morbidity and mortality, which is worsened by the increasing rates of antibiotic resistance. It is a constituent of the host microbiota of different mucosa, that can invade and cause infections in many different sites. The development of new treatments and prophylaxis against this pathogen rely on animal models to identify potential targets and evaluate the efficacy and possible side effects of therapeutic agents or vaccines. However, the validity of data generated is highly dependable on choosing models that can adequately reproduce the hallmarks of human diseases. The present review summarizes the current knowledge on animal models used to investigate K. pneumoniae infections, with a focus on mucosal sites. The advantages and limitations of each model are discussed and compared; the applications, extrapolations to human subjects and future modifications that can improve the current techniques are also presented. While mice are the most widely used species in K. pneumoniae animal studies, they present limitations such as the natural resistance to the pathogen and difficulties in reproducing the main steps of human mucosal infections. Other models, such as Drosophila melanogaster (fruit fly), Caenorhabditis elegans, Galleria mellonella and Danio rerio (zebrafish), contribute to understanding specific aspects of the infection process, such as bacterial lethality and colonization and innate immune system response, however, they but do not present the immunological complexity of mammals. In conclusion, the choice of the animal model of K. pneumoniae infection will depend mainly on the questions being addressed by the study, while a better understanding of the interplay between bacterial virulence factors and animal host responses will provide a deeper comprehension of the disease process and aid in the development of effective preventive/therapeutic strategies.

RESUMO

The CRISPR/Cas9 system is a simpler and more versatile method compared to other engineered nucleases such as Zinc Finger Nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs), and since its discovery, the efficiency of CRISPR-based genome editing has increased to the point that multiple and different types of edits can be made simultaneously. These advances in gene editing have revolutionized biotechnology by enabling precise genome editing with greater simplicity and efficacy than ever before. This tool has been successfully applied to a wide range of animal species, including cattle, pigs, dogs, and other small animals. Engineered nucleases cut the genome at specific target positions, triggering the cell's mechanisms to repair the damage and introduce a mutation to a specific genomic site. This review discusses novel genome-based CRISPR/Cas9 editing tools, methods developed to improve efficiency and specificity, the use of gene-editing on animal models and translational medicine, and the main challenges and limitations of CRISPR-based gene-editing approaches.