scholarly journals Critical evaluation of challenges and future use of animals in experimentation for biomedical research

2016 ◽  
Vol 29 (4) ◽  
pp. 551-561 ◽  
Author(s):  
Vijay Pal Singh ◽  
Kunal Pratap ◽  
Juhi Sinha ◽  
Koundinya Desiraju ◽  
Devika Bahal ◽  
...  

Animal experiments that are conducted worldwide contribute to significant findings and breakthroughs in the understanding of the underlying mechanisms of various diseases, bringing up appropriate clinical interventions. However, their predictive value is often low, leading to translational failure. Problems like translational failure of animal studies and poorly designed animal experiments lead to loss of animal lives and less translatable data which affect research outcomes ethically and economically. Due to increasing complexities in animal usage with changes in public perception and stringent guidelines, it is becoming difficult to use animals for conducting studies. This review deals with challenges like poor experimental design and ethical concerns and discusses key concepts like sample size, statistics in experimental design, humane endpoints, economic assessment, species difference, housing conditions, and systematic reviews and meta-analyses that are often neglected. If practiced, these strategies can refine the procedures effectively and help translate the outcomes efficiently.

Author(s):  
Adaya Weissler Snir ◽  
Kim A. Connelly ◽  
Jack M. Goodman ◽  
David Dorian ◽  
Paul Dorian

The detailed physiological consequences of aerobic training, in patients with hypertrophic cardiomyopathy (HCM) are not well understood. In athletes and non-athletes with HCM, there are two hypothetical concerns with respect to exercise: exercise-related worsening of the phenotype (e.g. promoting hypertrophy, fibrosis), and/or triggering of arrhythmia. The former concern is unproven and animal studies suggest an opposite effect, where exercise has been shown to be protective. The main reason for exercise restriction in HCM is fear of exercise-induced arrhythmia. Whilst the safety of sports in HCM has been reviewed, even more recent data suggest a substantially lower risk for sudden cardiac death (SCD) in HCM than previously thought, and there is an ongoing debate about restrictions of exercise imposed on individuals with HCM. This review outlines the pathophysiology of HCM, the impact of acute and chronic exercise (and variations of exercise intensity, modality, and athletic phenotype) in HCM including changes in autonomic function, blood pressure, cardiac dimensions and function, and cardiac output, and the underlying mechanisms that may trigger exercise-induced lethal arrhythmias. It provides a critical evaluation of the evidence regarding risk of SCD in athletes and the potential benefits of targeted exercise prescription in adults with HCM. Finally, it provides considerations for personalized recommendations for sports participation based on the available data.


Author(s):  
Zahra Bahadoran ◽  
Parvin Mirmiran ◽  
Khosrow Kashfi ◽  
Asghar Ghasemi

Results of animal experiments are used for understanding the pathophysiology of diseases, assessing safety and efficacy of newly developed drugs, and monitoring environmental health hazards among others. Systematic reviews and meta-analyses of animal data are important tools to condense animal evidence and translate the data into practical clinical applications. Such studies are conducted to explore heterogeneity, to generate new hypotheses about pathophysiology and treatment, to design new clinical trial modalities, and to test the efficacy and the safety of the various interventions. Here, we provide an overview regarding the importance of systematic reviews and meta-analyses of animal data and discuss common challenges and their potential solutions. Current evidence highlights various problems and challenges that surround these issues, including lack of generalizability of data obtained from animal models, failure in translating data obtained from animals to humans, poor experimental design and the reporting of the animal studies, heterogeneity of the data collected, and methodologic weaknesses of animal systematic reviews and meta-analyses. Systematic reviews and meta-analyses of animal studies can catalyze translational processes more effectively if they focus on a well-defined hypothesis along with addressing clear inclusion and exclusion criteria, publication bias, heterogeneity of the data, and a coherent and well-balanced assessment of studies' quality.


2021 ◽  
Vol 12 (2) ◽  
pp. 202-216
Author(s):  
Mus Azza Suhana Khairudin ◽  
Abbe Maleyki Mhd Jalil ◽  
Napisah Hussin

A diet high in polyphenols is associated with a diversified gut microbiome. Tea is the second most consumed beverage in the world, after water. The health benefits of tea might be attributed to the presence of polyphenol compounds such as flavonoids (e.g., catechins and epicatechins), theaflavins, and tannins. Although many studies have been conducted on tea, little is known of its effects on the trillions of gut microbiota. Hence, this review aimed to systematically study the effect of tea polyphenols on the stimulation or suppression of gut microbiota in humans and animals. It was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Articles were retrieved from PubMed and Scopus databases, and data were extracted from 6 human trials and 15 animal studies. Overall, large variations were observed in terms of microbiota composition between humans and animals. A more consistent pattern of diversified microbiota was observed in animal studies. Tea alleviated the gut microbiota imbalance caused by high-fat diet-induced obesity, diabetes, and ultraviolet-induced damage. The overall changes in microbiota composition measured by beta diversity analysis showed that tea had shifted the microbiota from the pattern seen in animals that received tea-free intervention. In humans, a prebiotic-like effect was observed toward the gut microbiota, but these results appeared in lower-quality studies. The beta diversity in human microbiota remains intact despite tea intervention; supplementation with different teas affects different types of bacterial taxa in the gut. These studies suggest that tea polyphenols may have a prebiotic effect in disease-induced animals and in a limited number of human interventions. Further intervention is needed to identify the mechanisms of action underlying the effects of tea on gut microbiota.


2014 ◽  
Vol 94 (4) ◽  
pp. 1027-1076 ◽  
Author(s):  
M. A. Hanson ◽  
P. D. Gluckman

Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention.


Author(s):  
Hossein Omidi-Ardali ◽  
Abolfazl Ghasemi Badi ◽  
Elham Saghaei ◽  
Hossein Amini-Khoei

AbstractObjectivesPrevious studies have suggested antidepressant properties for modafinil; however, the underlying mechanisms mediating the antidepressant effect of modafinil have not been well recognized in clinical and animal studies. Nitric oxide (NO) is involved in the pathophysiology of depression. We attempted to investigate the possible role of NO in the antidepressant-like effect of modafinil in mouse forced swimming test (FST) and tail suspension test (TST).MethodsThe antidepressant-like effect of modafinil (25, 50 and 75 mg/kg), alone and in combination with l-arginine, l-arg, (100 mg/kg) and NG-l-arginine methyl ester, l-NAME (5 mg/kg), was evaluated using FST and TST. Following behavioral tests, the hippocampi were dissected out to measure nitrite levels.ResultsFindings suggested that administration of modafinil at doses of 50 and 75 mg/kg significantly reduced immobility time in the FST and TST. Furthermore, administration of l-arg and l-NAME increased and decreased, respectively, the immobility time in the FST and TST. We showed that co-administration of a sub-effective dose of modafinil (25 mg/kg) plus l-NAME potentiated the antidepressant-like effect of the sub-effective dose of modafinil. In addition, co-treatment of an effective dose of modafinil (75 mg/kg) with l-arg attenuated the antidepressant-like effect of the effective dose of modafinil. We showed that the antidepressant-like effect of modafinil is associated with decreased nitrite levels in the hippocampus.ConclusionsOur findings for the first time support that the modulation of NO, partially at least, is involved in the antidepressant-like effect of modafinil in mouse FST and TST.


2016 ◽  
Vol 68 (Suppl. 2) ◽  
pp. 19-23 ◽  
Author(s):  
Daniel G. Bichet

Disorders of water balance are a common feature of clinical practice. An understanding of the physiology and pathophysiology of central vasopressin release and perception of thirst is the key to diagnosis and management of these disorders. Mammals are osmoregulators; they have evolved mechanisms that maintain extracellular fluid osmolality near a stable value, and, in animal studies, osmoregulatory neurons express a truncated delta-N variant of the transient receptor potential vannilloid (TRPV1) channel involved in hypertonicity and thermal perception while systemic hypotonicity might be perceived by TRPV4 channels. Recent cellular and optogenetic animal experiments demonstrate that, in addition to the multifactorial process of excretion, circumventricular organ sensors reacting to osmotic pressure and angiotensin II, subserve genesis of thirst, volume regulation and behavioral effects of thirst avoidance.


Author(s):  
Fábio C. Barbosa

Freight rail carriers have been continuously challenged to reduce costs and comply with increasingly stringent environmental standards, into a continuously competing and environmentally driven industry. In this context, current availability and relative abundance of clean and low cost non conventional gas reserves have aroused a comprehensive reevaluation of rail industry into fuel option, especially where freight rail are strongly diesel based. Countries in which rail sector is required to play an important role in transport matrix, where fuel expenditures currently accounts for a significant share of operational costs, like Australia, Brazil, United States and other continental countries, can be seen as strong candidates to adopt fuel alternatives to diesel fueled freight railways. Moreover, from an environmental perspective, the use of alternative fuels (like natural gas) for locomotive traction may allow rail freight carriers to comply with emission standards into a less technologically complex and costly way. In this context, liquefied natural gas (LNG) fueled freight locomotives are seen as a strong potential near-term driver for natural gas use in rail sector, with its intrinsic cost and environmental benefits and with the potential to revolutionize rail industry much like the transition from steam to diesel experienced into the fifties, as well as the more recent advent of use of alternating current diesel-electric locomotives. LNG rail fueled approach has been focused on both retrofitting existing locomotive diesel engines, as well as on original manufactured engines. Given the lower polluting potential of natural gas heavy engines, when compared to diesel counterparts, LNG locomotives can be used to comply with increasingly restrictive Particulate Matter (PM) and Nitrogen Oxides (NOx) emission standards with less technological complexity (engine design and aftertreatment hardware) and their intrinsic lower associated costs. Prior to commercial operation of LNG locomotives, there are some technical, operational and economic hurdles that need to be addressed, i.e. : i) locomotive engine and fuel tender car technological maturity and reliability improvement; ii) regulation improvement, basically focused on operational safety and interchange operations; iii) current and long term diesel - gas price differential, a decisive driver, and, finally, iv) LNG infrastructure requirements (fueling facilities, locomotives and tender car specifications). This work involved an extensive research into already published works to present an overview of LNG use in freight rail industry into a technical, operational and economical perspective, followed by a critical evaluation of its potential into some relevant freight rail markets, such as United States, Brazil and Australia, as well as some European non electrified rail freight lines.


Author(s):  
Jana Strahler ◽  
Hanna Wachten ◽  
Anett Mueller-Alcazar

AbstractBackgroundOrthorexia Nervosa (ON) and exercise addiction (ExAdd) are two phenomena believed to overlap. We conducted a meta-analysis exploring the link between ON and (addictive) exercise behaviors.MethodsA systematic review of major databases and gray literature was carried out for studies reporting on ON and (addictive) exercise behaviors. Random effects meta-analyses were undertaken calculating correlations between ON and (addictive) exercise behaviors. A sub-group analysis investigated gender differences.ResultsTwenty-five studies with 10,134 participants (mean age = 25.21; 56.4% female) were included. Analyses showed a small overall correlation between ON and exercise (21 studies, r = 0.12, 95% CI |0.06–0.18|) and a medium overall correlation between ON and ExAdd (7 studies, r = 0.29, 95% CI |0.13–0.45|). Gender differences were negligible.ConclusionsOrthorexic eating correlated slightly and moderately with exercise and ExAdd, respectively, expressing some unique and shared variance of these behaviors. While this does not suggest ON and addictive exercising to be independent, it does not indicate substantial comorbidity. Future research should focus on clinical relevance, underlying mechanisms, vulnerability, and risk factors.


2021 ◽  
Vol 64 (2) ◽  
Author(s):  
Ali Majlesara ◽  
Omid Ghamarnejad ◽  
Elias Khajeh ◽  
Mohammad Golriz ◽  
Negin Gharabaghi ◽  
...  

Background: Portal vein arterialization (PVA) is a possible option when hepatic artery reconstruction is impossible during liver resection. The aim of this study was to review the literature on the clinical application of PVA in hepatopancreatobiliary (HPB) surgery. Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched the PubMed, Embase and Web of Science databases until December 2019. Experimental (animal) studies, review articles and letters were excluded. Results: Twenty studies involving 57 patients were included. Cholangiocarcinoma was the most common indication for surgery (40 patients [74%]). An end-to-side anastomosis between a celiac trunk branch and the portal vein was the main PVA technique (35 patients [59%]). Portal hypertension was the most common longterm complication (12 patients [21%] after a mean of 4.1 mo). The median followup period was 12 (range 1–87) months. The 1-, 3- and 5-year survival rates were 64%, 27% and 20%, respectively. Conclusion: Portal vein arterialization can be considered as a rescue option to improve the outcome in patients with acute liver de-arterialization when arterial reconstruction is not possible. To prevent portal hypertension and liver injuries due to thrombosis or overarterialization, vessel calibre adjustment and timely closure of the anastomosis should be considered. Further prospective experimental and clinical studies are needed to investigate the potential of this procedure in patients whose liver is suddenly de-arterialized during HPB procedures.


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