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Brain Circulation 2022Ischemic stroke is a disease with worldwide economic and social negative effects. It is a serious disease with high disability and mortality. Ionic imbalance,... (Review)
Review
Ischemic stroke is a disease with worldwide economic and social negative effects. It is a serious disease with high disability and mortality. Ionic imbalance, excitotoxicity, oxidative stress, and inflammation are induced during and after ischemic stroke. Cellular dysfunction, apoptosis, and necrosis are activated directly or indirectly mechanisms. The studies about neuroprotection in neurodegenerative diseases have increased in recent years. Data about the mechanisms of progressive molecular improvement in the brain tissue are increasing in acute ischemic stroke. Based on these data, preclinical and clinical studies on new neuroprotective treatments are being designed. An effective neuroprotective strategy can prolong the indication period of recanalization treatments in the acute stage of ischemic stroke. In addition, it can reduce neuronal necrosis and protect the brain against ischemia-related reperfusion injury. The current review has evaluated the recent clinical and experimental studies. The molecular mechanism of each of the neuroprotective strategies is also summarized. This review may help develop future strategies for combination treatment to protect the cerebral tissue from ischemia-reperfusion injury.
PubMed: 37181847
DOI: 10.4103/bc.bc_52_22 -
Clinical Rheumatology Jan 2022Corticosteroid-sparing disease-modifying anti-rheumatic drugs are an area of active exploration in large vessel vasculitis (LVV), i.e., Takayasu arteritis (TAK) and... (Review)
Review
Corticosteroid-sparing disease-modifying anti-rheumatic drugs are an area of active exploration in large vessel vasculitis (LVV), i.e., Takayasu arteritis (TAK) and Giant Cell Arteritis (GCA). The role of Janus kinase (JAK) inhibitors has been recently identified in different inflammatory rheumatic diseases. We conducted a systematic review of the use of JAK inhibitors in LVV across MEDLINE, Scopus, Web of Science, EMBASE, PubMed Central, Cochrane database of controlled trials, clinicaltrials.gov, and major recent international conferences. We identified four cohort studies and ten case reports. The JAK inhibitors used in these studies were tofacitinib, baricitinib, and ruxolitinib. A cohort study in TAK compared 27 patients treated with tofacitinib with 26 others treated with methotrexate, with better clinical outcomes with tofacitinib but similar angiographic stabilization, relapses, corticosteroid-sparing effect, and adverse events in both groups. Most of the other studies favored clinical responses with JAK inhibitors in LVV but with a paucity of data on other outcomes. Most of the included studies were of moderate quality. Evidence from pre-clinical models of LVV as well as limited in vivo data in patients with TAK appears to suggest that JAK inhibition reduces adventitial fibrosis, intimal proliferation, and inflammatory T lymphocyte infiltration in the media as well as reduces resident memory T cells in the vascular wall (which are otherwise resistant to corticosteroids). Ongoing clinical trials of tofacitinib, baricitinib, and upadacitinib in LVV shall help to further clarify the potential promise of JAK inhibitors for LVV (PROSPERO registration number CRD42021273359). KEY POINTS : •Tofacitinib appeared to associate with better clinical outcomes than methotrexate in TAK. •JAKinibs reduce adventitial fibrosis, intimal proliferation, and inflammatory vascular infiltrate in pre-clinical models of LVV. •Tofacitinib downregulates resident memory vascular T lymphocytes in pre-clinical models of LVV.
Topics: Antirheumatic Agents; Cohort Studies; Giant Cell Arteritis; Humans; Janus Kinase Inhibitors; Memory T Cells; Takayasu Arteritis
PubMed: 34729652
DOI: 10.1007/s10067-021-05973-4 -
Viruses Nov 2022The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review... (Review)
Review
The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review research done on preclinical studies focusing on the potential monkeypox treatment and immunization. The presented juxtaposition of efficacy of potential treatments and vaccination that had been tested in preclinical trials could serve as a useful primer of monkeypox virus. The literature identified using key terms such as monkeypox virus or management or vaccine stringed using Boolean operators was systematically reviewed. Pubmed, SCOPUS, Cochrane, and preprint databases were used, and screening was performed in accordance with PRISMA guidelines. A total of 467 results from registered databases and 116 from grey literature databases were screened. Of these results, 72 studies from registered databases and three grey literature studies underwent full-text screening for eligibility. In this systematic review, a total of 27 articles were eligible according to the inclusion criteria and were used. Tecovirimat, known as TPOXX or ST-246, is an antiviral drug indicated for smallpox infection whereas brincidofovir inhibits the viral DNA polymerase after incorporation into viral DNA. The ability of tecovirimat in providing protection to poxvirus-challenged animals from death had been demonstrated in a number of animal studies. Non-inferior with regard to immunogenicity was reported for the live smallpox/monkeypox vaccine compared with a single dose of a licensed live smallpox vaccine. The trial involving the live vaccine showed a geometric mean titre of vaccinia-neutralizing antibodies post two weeks of the second dose of the live smallpox/monkeypox vaccine. Of note, up to the third generation of smallpox vaccines-particularly JYNNEOS and Lc16m8-have been developed as preventive measures for MPXV infection and these vaccines had been demonstrated to have improved safety compared to the earlier generations.
Topics: Animals; Humans; Mpox (monkeypox); Smallpox Vaccine; Smallpox; Pandemics; COVID-19; Monkeypox virus; Variola virus; Vaccinia virus; Vaccines, Attenuated; COVID-19 Drug Treatment
PubMed: 36423105
DOI: 10.3390/v14112496 -
Pain Apr 2020Despite large efforts to test analgesics in animal models, only a handful of new pain drugs have shown efficacy in patients. Here, we report a systematic review and... (Meta-Analysis)
Meta-Analysis
Despite large efforts to test analgesics in animal models, only a handful of new pain drugs have shown efficacy in patients. Here, we report a systematic review and meta-analysis of preclinical studies of the commercially successful drug pregabalin. Our primary objective was to describe design characteristics and outcomes of studies testing the efficacy of pregabalin in behavioral models of pain. Secondarily, we examined the relationship between design characteristics and effect sizes. We queried MEDLINE, Embase, and BIOSIS to identify all animal studies testing the efficacy of pregabalin published before January 2018 and recorded experimental design elements addressing threats to validity and all necessary data for calculating effect sizes, expressed as the percentage of maximum possible effect. We identified 204 studies (531 experiments) assessing the efficacy of pregabalin in behavioral models of pain. The analgesic effect of pregabalin was consistently robust across every etiology/measure tested, even for pain conditions that have not responded to pregabalin in patients. Experiments did not generally report using design elements aimed at reducing threats to validity, and analgesic activity was typically tested in a small number of model systems. However, we were unable to show any clear relationships between preclinical design characteristics and effect sizes. Our findings suggest opportunities for improving the design and reporting of preclinical studies in pain. They also suggest that factors other than those explored in this study may be more important for explaining the discordance between outcomes in animal models of pain and those in clinical trials.
Topics: Analgesics; Animals; Humans; Pain; Pregabalin
PubMed: 31977931
DOI: 10.1097/j.pain.0000000000001749 -
Investigative Ophthalmology & Visual... Dec 2017To provide a comprehensive and current review on the available experimental animal models of retinal vein occlusion (RVO) and to identify their strengths and limitations... (Review)
Review
PURPOSE
To provide a comprehensive and current review on the available experimental animal models of retinal vein occlusion (RVO) and to identify their strengths and limitations with the purpose of helping researchers to plan preclinical studies on RVO.
METHODS
A systematic review of the literature on experimental animal models of RVO was undertaken. Medline, SCOPUS, and Web of Science databases were searched. Studies published between January 1, 1965, and March 31, 2017, and that met the inclusion criteria were reviewed. The data extracted included animal species used, methods of inducing RVO, and the clinical and histopathologic features of the models, especially in relation to strengths, limitations, and faithfulness to clinical sequelae.
RESULTS
A total of 128 articles fulfilling the inclusion criteria were included. Several species were used to model human branch and central RVO (BRVO; CRVO) with nonhuman primates being the most common, followed by rodents and pigs. BRVO and CRVO were most commonly induced by laser photocoagulation and all models showed early features of clinical disease, including retinal hemorrhages and retinal edema. These features made many of the models adequate for studying the acute phase of BRVO and CRVO, although macular edema, retinal ischemia, and neovascular complications were observed in only a few experimental animal models (laser-induced model in rodents, pigs, and nonhuman primates, diathermy-induced model in pigs, and following intravitreal injection of PD0325901 in rabbits for BRVO; and in the laser-induced model in rodents, rabbits, and nonhuman primates, diathermy-induced model in nonhuman primates, following permanent ligation of the central retinal vein in nonhuman primates, and with intravitreal injection of thrombin in rabbits for CRVO).
CONCLUSIONS
Experimental animal models of RVO are available to study the pathogenesis of this disease and to evaluate diagnostic/prognostic biomarkers and to develop new therapeutics. Data available suggest laser-induced RVO in pigs and rodents to be overall the best models of BRVO and the laser-induced RVO rodents the best model for CRVO.
Topics: Animals; Disease Models, Animal; Prognosis; Retinal Vein Occlusion; Visual Acuity
PubMed: 29222552
DOI: 10.1167/iovs.17-22788 -
Pharmacological Research Nov 2022As the worldwide population progresses in age, there is an increasing need for effective treatments for age-associated musculoskeletal conditions such as osteoporosis... (Review)
Review
As the worldwide population progresses in age, there is an increasing need for effective treatments for age-associated musculoskeletal conditions such as osteoporosis and osteoarthritis (OA). Fisetin, a natural flavonoid, has garnered attention as a promising pharmaceutical option for treating or delaying the progression of osteoporosis and OA. However, there is no systematic review of the effects of fisetin on bone and cartilage. The aim of this review is to report the latest evidence on the effects of fisetin on bone and cartilage, with a focus on clinical significance. The PubMed, Embase, and Cochrane Library databases were searched up to December 9th 2021 to evaluate the effects of fisetin on bone and cartilage in in vitro studies and in vivo preclinical animal studies. The risk of bias, quality, study design, sample characteristics, dose and duration of fisetin treatment, and outcomes of the 13 eligible studies were analyzed in this systematic review. Qualitative evaluation was conducted for each study due to differences in animal species, cell type, created disease model, dose and duration of fisetin treatment, and time between intervention and assessment among the eligible studies. The beneficial effects of fisetin on osteoporosis have been demonstrated in in vitro and in vivo preclinical studies across animal species. Similarly, the beneficial effects of fisetin on OA have been demonstrated in in vivo preclinical animal studies, but the reports on OA are still limited. Fisetin, a natural supplement can be use in orthobiologics treatment, as adjuvant to orthopaedic surgery, to improve clinical outcome.
Topics: Animals; Flavonols; Osteoarthritis; Osteoporosis; Cartilage
PubMed: 36243333
DOI: 10.1016/j.phrs.2022.106504 -
Adolescent Psychiatry (Hilversum,... 2023Adolescents and young adults may use cannabidiol (CBD) products in an attempt to reduce depression and anxiety symptoms, despite little research examining this use. This...
BACKGROUND
Adolescents and young adults may use cannabidiol (CBD) products in an attempt to reduce depression and anxiety symptoms, despite little research examining this use. This systematic review evaluated preclinical and clinical research on the effects of CBD on depressive and anxiety disorders in adolescence and young adulthood. To provide context, we discuss CBD's mechanism of action and neurodevelopmental effects.
METHODS
PubMed was searched for articles published through June 2022. Preclinical or clinical CBD administration studies with > 1 that examined depressive and/or anxiety disorders were eligible.
RESULTS
Initially, 224 publications were identified. After excluding duplicates and applying eligibility criteria, 6 preclinical (depression: ≈133; anxiety: ≈161) and 4 clinical (anxiety: =113) articles remained. Due to the low number of studies, results were synthesized qualitatively. The Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence were used to rate each study's evidence. The preclinical effects of CBD on depression-like behavior appear to differ by sex, early life stress, and duration of use. Despite no evidence that CBD exerts anxiolytic effects in preclinical adolescent models, CBD may reduce anxiety symptoms in human adolescents and young adults with anxiety disorders.
CONCLUSIONS
The existing evidence suggests that CBD may reduce symptoms of anxiety in adolescents and young adults. However, the evidence is sparse and limited by variations in samples and CBD dosing duration. Further research is needed to understand the potential benefits and/or harms of CBD for depression and anxiety disorders in this population. Implications for clinical practice and research are discussed.
PubMed: 38919887
DOI: 10.2174/0122106766233339230919143924 -
Antibiotic-induced gut dysbiosis and autoimmune disease: A systematic review of preclinical studies.Autoimmunity Reviews Sep 2022Antibiotic-induced gut dysbiosis is believed to be associated with the onset and development of autoimmune diseases. To evaluate microbiota's variations triggered by... (Review)
Review
Antibiotic-induced gut dysbiosis is believed to be associated with the onset and development of autoimmune diseases. To evaluate microbiota's variations triggered by antibiotic therapy and its outcomes on autoimmune diseases, preclinical studies regarding these subjects were included in this review. The studies were selected on PubMed, Scopus and Web of Science from 2011 to 2021 by three researchers that extracted study data and risk of bias, which were verified by a further 3 independent researchers. The team assessed the strength of evidence across studies. Of the eligible studies, 17 showed an improvement of the studied disease after antibiotic therapy and 10 had a negative effect on the course of the condition. The ameliorating factors of the studied diseases were mostly seen when using an antibiotic cocktail. Male animals had a good outcome after therapy and, for all genders, the increase in IL-10 and Treg cells was often shown to ameliorate disease after the antibiotic intervention. Firmicutes, Proteobacteria and Bacteroidetes appeared altered after the antibiotic intervention, leading to amelioration or worsening of the condition depending on the autoimmune disease. We identified that the number of autoimmune conditions approached leads to specific conclusions regarding the interventions, making it difficult to achieve an overall conclusion. Overall, even though pre-clinical studies must be translated to the human model, the studied aspects of gender, age, lineage and disease model substantially impact the outcomes that make for many intricacies that were not-established in the study of antibiotic-induced gut dysbiosis and autoimmunity.
Topics: Animals; Anti-Bacterial Agents; Autoimmune Diseases; Bacteroidetes; Dysbiosis; Female; Gastrointestinal Microbiome; Humans; Male
PubMed: 35830954
DOI: 10.1016/j.autrev.2022.103140 -
Human Psychopharmacology Mar 2015Lithium treatment remains an important part of the management of many patients with bipolar disorder, but the incidence of treatment-emergent sexual dysfunction with... (Review)
Review
OBJECTIVE
Lithium treatment remains an important part of the management of many patients with bipolar disorder, but the incidence of treatment-emergent sexual dysfunction with lithium is uncertain, and little is known about how it might be managed.
METHOD
Systematic computerised literature search of preclinical and clinical studies.
RESULTS
Thirteen relevant papers were identified. Preclinical studies suggest lithium can reduce testosterone levels and impair nitric oxide mediated relaxation of cavernosal tissue. Clinical reports suggest lithium may reduce sexual thoughts and desire, worsen erectile function and reduce sexual satisfaction. Concomitant benzodiazepine prescription with lithium is associated with an increased risk of sexual dysfunction. Sexual dysfunction during lithium treatment appears significantly associated with a lower level of overall functioning and may reduce compliance.
CONCLUSION
The findings of this systematic review reveal the paucity of information about the incidence, associated factors and management of sexual dysfunction with lithium treatment and highlight the need for well-designed studies in this area.
Topics: Animals; Antidepressive Agents; Bipolar Disorder; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Lithium; PubMed; Sexual Dysfunction, Physiological
PubMed: 25619161
DOI: 10.1002/hup.2457 -
Aesthetic Plastic Surgery Apr 2016Autologous lipotransfer is seen as an ideal filler for soft tissue reconstruction. The main limitation of this procedure is the unpredictable resorption and volume loss... (Review)
Review
INTRODUCTION
Autologous lipotransfer is seen as an ideal filler for soft tissue reconstruction. The main limitation of this procedure is the unpredictable resorption and volume loss of the fat graft. In the recent decade, an increasing amount of research has focused on the use of adipose tissue-derived stromal cells (ASCs) to enrich the fat graft, a procedure termed cell-assisted lipotransfer (CAL). The aim of this review was to systematically review the current preclinical and clinical evidence for the efficacy of CAL compared with conventional lipotransfer.
MATERIALS AND METHODS
A systematic search was performed on PubMed and other databases to identify all preclinical and clinical studies where CAL with ASCs was compared with conventional lipotransfer. A total of 20 preclinical studies and seven clinical studies were included in the review.
RESULTS
The preclinical studies consisted of 15 studies using immunodeficient animal models and five studies using immunocompetent studies. Seventeen studies examined weight/volume retention of which 15 studies favored CAL over conventional lipotransfer. One clinical study did not find any efficacy of CAL and the remaining six studies favored CAL.
CONCLUSIONS
The present evidence suggests that there is a big potential for CAL in reconstructive surgery; however, the present studies are so far still of low quality with inherent weaknesses. Several aspects regarding CAL still remain unknown such as the optimal degree of cell enrichment and also its safety. Further high-quality studies are needed to establish if CAL can live up to its potential.
LEVEL OF EVIDENCE V
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Topics: Adipocytes; Adipose Tissue; Animals; Clinical Trials as Topic; Disease Models, Animal; Humans; Plastic Surgery Procedures; Stromal Cells
PubMed: 26893280
DOI: 10.1007/s00266-016-0613-1