Application of New Therapies in Graves' Disease and Thyroid-Associated Ophthalmopathy: Animal Models and Translation to Human Clinical Trials

Thyroid ◽  
2008 ◽  
Vol 18 (9) ◽  
pp. 973-981 ◽  
Author(s):  
J. Paul Banga ◽  
Claus H. Nielsen ◽  
Jacqueline A. Gilbert ◽  
Daniel El Fassi ◽  
Laszlo Hegedus
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Graves Disease ◽  
New Therapies ◽  
Thyroid Associated Ophthalmopathy

Berberine: A Promising Natural Isoquinoline Alkaloid for the Development of Hypolipidemic Drugs

2020 ◽  
Vol 20 (28) ◽  
pp. 2634-2647
Author(s):  
Dong-Dong Li ◽  
Pan Yu ◽  
Wei Xiao ◽  
Zhen-Zhong Wang ◽  
Lin-Guo Zhao
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Physicochemical Properties ◽  
Isoquinoline Alkaloid ◽  
Hypolipidemic Activity ◽  
Lipid Lowering ◽  
Lipid Lowering Drug ◽  
Lipid Lowering Agent ◽  
Lowering Drug ◽  
Hypolipidemic Drugs

: Berberine, as a representative isoquinoline alkaloid, exhibits significant hypolipidemic activity in both animal models and clinical trials. Recently, a large number of studies on the lipid-lowering mechanism of berberine and studies for improving its hypolipidemic activity have been reported, but for the most part, they have been either incomplete or not comprehensive. In addition, there have been a few specific reviews on the lipid-reducing effect of berberine. In this paper, the physicochemical properties, the lipid-lowering mechanism, and studies of the modification of berberine all are discussed to promote the development of berberine as a lipid-lowering agent. Subsequently, this paper provides some insights into the deficiencies of berberine in the study of lipid-lowering drug, and based on the situation, some proposals are put forward.

scholarly journals Inflammation and Atherosclerosis

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1197
Author(s):  
Klaus Ley
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Basic Science ◽  
Translational Science ◽  
Special Issue

This 11-chapter Special Issue of Cells spans the gamut from basic science in mechanistic animal models to translational science to outcomes of clinical trials, all focused on the role of inflammation in atherosclerosis [...]

Extracorporeal shockwave therapy in spinal cord injury, early to advance to clinical trials? A systematic review and meta-analysis on animal studies

2021 ◽  
pp. 197140092110268
Author(s):  
Seyedeh Niloufar Rafiei Alavi ◽  
Arian Madani Neishaboori ◽  
Mahmoud Yousefifard
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Animal Models ◽  
Meta Analysis ◽  
Mean Difference ◽  
Extracorporeal Shockwave Therapy ◽  
Extracorporeal Shockwave ◽  
Shockwave Therapy ◽  
Cord Injury

Background As there is no consensus over the efficacy of extracorporeal shockwave therapy in the management of spinal cord injury complications, the current meta-analysis aims to investigate preclinical evidence on the matter. Methods The search strategy was developed based on keywords related to ‘spinal cord injury’ and ‘extracorporeal shockwave therapy’. A primary search was conducted in Medline, Embase, Scopus and Web of Science until the end of 2020. Studies which administered extracorporeal shockwave therapy on spinal cord injury animal models and evaluated motor function and/or histological findings were included. The standardised mean difference with a 95% confidence interval (CI) were calculated. Results Seven articles were included. Locomotion was significantly improved in the extracorporeal shockwave therapy treated group (standardised mean difference 1.68, 95% CI 1.05–2.31, P=0.032). It seems that the efficacy of extracorporeal shockwave therapy with an energy flux density of 0.1 mJ/mm2 is higher than 0.04 mJ/mm2 ( P=0.044). Shockwave therapy was found to increase axonal sprouting (standardised mean difference 1.31, 95% CI 0.65, 1.96), vascular endothelial growth factor tissue levels (standardised mean difference 1.36, 95% CI 0.54, 2.18) and cell survival (standardised mean difference 2.49, 95% CI 0.93, 4.04). It also significantly prevents axonal degeneration (standardised mean difference 2.25, 95% CI 1.47, 3.02). Conclusion Extracorporeal shockwave therapy significantly improves locomotor recovery in spinal cord injury animal models through neural tissue regeneration. Nonetheless, in spite of the promising results and clinical application of extracorporeal shockwave therapy in various conditions, current evidence implies that designing clinical trials on extracorporeal shockwave therapy in the management of spinal cord injury may not be soon. Hence, further preclinical studies with the effort to reach the safest and the most efficient treatment protocol are needed.

scholarly journals Intraoperative hypothermia during vascular neurosurgical procedures

2009 ◽  
Vol 26 (5) ◽  
pp. E24 ◽  
Author(s):  
Raymond Choi ◽  
Robert H. Andres ◽  
Gary K. Steinberg ◽  
Raphael Guzman
Keyword(s):  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
Animal Models ◽  
Mild Hypothermia ◽  
Scientific Evidence ◽  
Neurosurgical Procedures ◽  
Ischemic Damage ◽  
Intraoperative Hypothermia ◽  
Improved Outcomes

Increasing evidence in animal models and clinical trials for stroke, hypoxic encephalopathy for children, and traumatic brain injury have shown that mild hypothermia may attenuate ischemic damage and improve neurological outcome. However, it is less clear if mild intraoperative hypothermia during vascular neurosurgical procedures results in improved outcomes for patients. This review examines the scientific evidence behind hypothermia as a treatment and discusses factors that may be important for the use of this adjuvant technique, including cooling temperature, duration of hypothermia, and rate of rewarming.

scholarly journals Efficacy of Nitazoxanide againstCryptosporidium parvum in Cell Culture and in Animal Models

1998 ◽  
Vol 42 (8) ◽  
pp. 1959-1965 ◽  
Author(s):  
Cynthia M. Theodos ◽  
Jeffrey K. Griffiths ◽  
Jennifer D’Onfro ◽  
Alexandra Fairfield ◽  
Saul Tzipori
Keyword(s):  
Cell Culture ◽  
Clinical Trials ◽  
Body Weight ◽  
Animal Models ◽  
Cryptosporidium Parvum ◽  
Combined Treatment ◽  
Parasite Burden ◽  
Parasite Growth ◽  
Gnotobiotic Piglet

ABSTRACT Nitazoxanide (NTZ), a drug currently being tested in human clinical trials for efficacy against chronic cryptosporidiosis, was assessed in cell culture and in two animal models. The inhibitory activity of NTZ was compared with that of paromomycin (PRM), a drug that is partially effective against Cryptosporidium parvum. A concentration of 10 μg of NTZ/ml (32 μM) consistently reduced parasite growth in cell culture by more than 90% with little evidence of drug-associated cytotoxicity, in contrast to an 80% reduction produced by PRM at 2,000 μg/ml (3.2 mM). In contrast to its efficacy in vitro, NTZ at either 100 or 200 mg/kg of body weight/day for 10 days was ineffective at reducing the parasite burden in C. parvum-infected, anti-gamma-interferon-conditioned SCID mice. Combined treatment with NTZ and PRM was no more effective than treatment with PRM alone. Finally, NTZ was partially effective at reducing the parasite burden in a gnotobiotic piglet diarrhea model when given orally for 11 days at 250 mg/kg/day but not at 125 mg/kg/day. However, the higher dose of NTZ induced a drug-related diarrhea in piglets that might have influenced its therapeutic efficacy. As we have previously reported, PRM was effective at markedly reducing the parasite burden in piglets at a dosage of 500 mg/kg/day. Our results indicate that of all of the models tested, the piglet diarrhea model most closely mimics the partial response to NTZ treatment reported to occur in patients with chronic cryptosporidiosis.

scholarly journals New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy

2021 ◽  
Author(s):  
Suresh Victor ◽  
Eridan Rocha-Ferreira ◽  
Ahad Rahim ◽  
Henrik Hagberg ◽  
David Edwards
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Therapeutic Hypothermia ◽  
Treatment Options ◽  
Standard Of Care ◽  
High Income ◽  
Hypoxic Ischemic Encephalopathy ◽  
Pharmacodynamic Modelling ◽  
Dose Ranging ◽  
Ischemic Encephalopathy

AbstractAround 0.75 million babies worldwide suffer from moderate or severe hypoxic-ischemic encephalopathy (HIE) each year resulting in around 400,000 babies with neurodevelopmental impairment. In 2010, neonatal HIE was associated with 2.4% of the total Global Burden of Disease. Therapeutic hypothermia (TH), a treatment that is now standard of care in high-income countries, provides proof of concept that strategies that aim to improve neurodevelopment are not only possible but can also be implemented to clinical practice. While TH is beneficial, neonates with moderate or severe HIE treated with TH still experience devastating complications: 48% (range: 44–53) combined death or moderate/severe disability. There is a concern that TH may not be effective in low- and middle-income countries. Therapies that further improve outcomes are desperately needed, and in high-income countries, they must be tested in conjunction with TH. We have in this review focussed on pharmacological treatment options (e.g. erythropoietin, allopurinol, melatonin, cannabidiol, exendin-4/exenatide). Erythropoietin and allopurinol show promise and are progressing towards the clinic with ongoing definitive phase 3 randomised placebo-controlled trials. However, there remain global challenges for the next decade. Conclusion: There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials to avoid exposure to harmful medications or abandoning putative treatments. What is Known:• Therapeutic hypothermia is beneficial in neonatal hypoxic-ischemic encephalopathy.• Neonates with moderate or severe hypoxic-ischemic encephalopathy treated with therapeutic hypothermia still experience severe sequelae. What is New:• Erythropoietin, allopurinol, melatonin, cannabidiol, and exendin-4/exenatide show promise in conjunction with therapeutic hypothermia.• There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials.

scholarly journals Using magnetic resonance imaging in animal models to guide drug development in multiple sclerosis

2013 ◽  
Vol 20 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Nabeela Nathoo ◽  
V Wee Yong ◽  
Jeff F Dunn
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Magnetic Resonance ◽  
Animal Models ◽  
Mr Imaging ◽  
Preclinical Studies ◽  
Resonance Imaging ◽  
Magnetic Resonance Imaging Mri ◽  
Potential Therapeutics

Major advances are taking place in the development of therapeutics for multiple sclerosis (MS), with a move past traditional immunomodulatory/immunosuppressive therapies toward medications aimed at promoting remyelination or neuroprotection. With an increase in diversity of MS therapies comes the need to assess the effectiveness of such therapies. Magnetic resonance imaging (MRI) is one of the main tools used to evaluate the effectiveness of MS therapeutics in clinical trials. As all new therapeutics for MS are tested in animal models first, it is logical that MRI be incorporated into preclinical studies assessing therapeutics. Here, we review key papers showing how MR imaging has been combined with a range of animal models to evaluate potential therapeutics for MS. We also advise on how to maximize the potential for incorporating MRI into preclinical studies evaluating possible therapeutics for MS, which should improve the likelihood of discovering new medications for the condition.

scholarly journals Towards Safer Treatments for Benign Anorectal Disease: The Pharmacological Manipulation of the Internal Anal Sphincter

2007 ◽  
Vol 89 (6) ◽  
pp. 574-579 ◽  
Author(s):  
Oliver M Jones
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Anal Fissure ◽  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Small Scale ◽  
Organ Bath ◽  
Vitro Analysis ◽  
In Vitro Analysis

INTRODUCTION The internal anal sphincter (IAS) is an important structure that is responsible for the majority of resting tone of the sphincter complex. It has a central role in continence and damage to the muscle has serious implications. Injury is most frequently from obstetric trauma though iatrogenic injury from proctological surgery is also common. This review expands on how developments in understanding of the pharmacology of IAS might identify drug treatments as alternatives for proctological conditions such as anal fissure, avoiding the risk of sphincter injury. It also examines the role of pharmacology in treatment of those patients with established incontinence. RESULTS Much of the basic physiology and pharmacology of the IAS has been established through in vitro analysis, particularly in the superfusion organ bath. Further analysis has been undertaken using animal models such the pig. Clinical trials have established the efficacy of a number of agents for reducing IAS tone including glyceryl trinitrate and botulinum toxin. These drugs are probably safer, but less effective, than surgery for sphincter spasm, as is seen in anal fissure, though surgery alone or in combination with drug treatment may be appropriate for some patients. In vitro analysis and small-scale clinical trials suggest that phenylephrine and methoxamine may have a role in treating patients with incontinence primarily attributable to inadequate IAS function. CONCLUSIONS The pharmacology of IAS has been extensively studied in the laboratory, both in vitro and in animal models. In a short time, this laboratory work has been applied to clinical problems after testing in clinical trials. It is likely, however, that the best drugs and the optimal targets for manipulation have not yet been identified.

scholarly journals Peptide hormone relaxin: from bench to bedside

2018 ◽  
Vol 314 (6) ◽  
pp. R753-R760 ◽  
Author(s):  
Maria Jelinic ◽  
Sarah A. Marshall ◽  
Dennis Stewart ◽  
Elaine Unemori ◽  
Laura J. Parry ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Animal Studies ◽  
Ischemia Reperfusion ◽  
Peptide Hormone ◽  
The Body ◽  
Cervical Ripening ◽  
Matrix Remodeling ◽  
Vitro Fertilization

The peptide hormone relaxin has numerous roles both within and independent of pregnancy and is often thought of as a “pleiotropic hormone.” Relaxin targets several tissues throughout the body, and has many functions associated with extracellular matrix remodeling and the vasculature. This review considers the potential therapeutic applications of relaxin in cervical ripening, in vitro fertilization, preeclampsia, acute heart failure, ischemia-reperfusion, and cirrhosis. We first outline the animal models used in preclinical studies to progress relaxin into clinical trials and then discuss the findings from these studies. In many cases, the positive outcomes from preclinical animal studies were not replicated in human clinical trials. Therefore, the focus of this review is to evaluate the various animal models used to develop relaxin as a potential therapeutic and consider the limitations that must be addressed in future studies. These include the use of human relaxin in animals, duration of relaxin treatment, and the appropriateness of the clinical conditions being considered for relaxin therapy.

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