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.

scholarly journals Potential roles of mitochondrial cofactors in the adjuvant mitigation of proinflammatory acute infections, as in the case of sepsis and COVID-19 pneumonia

2020 ◽  
Author(s):  
Giovanni Pagano ◽  
Carla Manfredi ◽  
Federico V. Pallardó ◽  
Alex Lyakhovich ◽  
Luca Tiano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Animal Studies ◽  
The Body ◽  
Acute Infections ◽  
Protective Actions ◽  
Chronic Disorders ◽  
State Of Art

Abstract Background The mitochondrial cofactors α-lipoic acid (ALA), coenzyme Q10 (CoQ10) and carnitine (CARN) play distinct and complementary roles in mitochondrial functioning, along with strong antioxidant actions. Also termed mitochondrial nutrients (MNs), these cofactors have demonstrated specific protective actions in a number of chronic disorders, as assessed in a well-established body of literature. Methods Using PubMed, the authors searched for articles containing information on the utilization of MNs in inflammatory disorders as assessed from in vitro and animal studies, and in clinical trials, in terms of exerting anti-inflammatory actions. Results The retrieved literature provided evidence relating acute pathologic conditions, such as sepsis and pneumonia, with a number of redox endpoints of biological and clinical relevance. Among these findings, both ALA and CARN were effective in counteracting inflammation-associated redox biomarkers, while CoQ10 showed decreased levels in proinflammatory conditions. MN-associated antioxidant actions were applied in a number of acute disorders, mostly using one MN. The body of literature assessing the safety and the complementary roles of MNs taken together suggests an adjuvant role of MN combinations in counteracting oxidative stress in sepsis and other acute disorders, including COVID-19-associated pneumonia. Conclusions The present state of art in the use of individual MNs in acute disorders suggests planning adjuvant therapy trials utilizing MN combinations aimed at counteracting proinflammatory conditions, as in the case of pneumonia and the COVID-19 pandemic.

scholarly journals Hydroxychloroquine/Chloroquine in COVID-19 With Focus on Hospitalized Patients - A Systematic Review

2022 ◽  
Author(s):  
Daniel Freilich ◽  
Jennifer Victory ◽  
Anne Gadomski
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Animal Studies ◽  
Randomized Clinical Trials ◽  
Hospitalized Patients ◽  
Safety Issues ◽  
Meta Analyses ◽  
In The Beginning ◽  
Almost All

Background In the beginning of the COVID-19 pandemic, many hospitalized patients received empiric hydroxychloroquine/chloroquine (HC/CQ). Although some retrospective-observational trials suggested potential benefit, all subsequent randomized clinical trials (RCTs) failed to show benefit and use generally ceased. Herein, we summarize key studies that clinicians advising patients on HC/CQ efficacy:safety calculus in hospitalized COVID-19 patients would want to know about in a practical one-stop-shopping source. Methods Pubmed and Google were searched on November 4, 2021. Search words included: COVID-19, hydroxychloroquine, chloroquine, in vitro, animal studies, clinical trials, and meta-analyses. Studies were assessed for import and included if considered impactful for benefit:risk assessment. Results These searches led to inclusion of 12 in vitro and animal reports; 12 retrospective-observational trials, 19 interventional clinical trials (17 RCTs, 1 single-arm, 1 controlled but unblinded), and 51 meta-analyses in hospitalized patients. Inconsistent efficacy was seen in vitro and in animal studies for coronaviruses and nil in SARS-CoV-2 animal models specifically. Most retrospective-observational studies in hospitalized COVID-19 patients found no efficacy; QT prolongation and increased adverse events and mortality were reported in some. All RCTs and almost all meta-analyses provided robust data showing no benefit in overall populations and subgroups, yet concerning safety issues in many. Conclusions HC/CQ have inconsistent anti-coronavirus efficacy in vitro and in animal models, and no convincing efficacy yet substantial safety issues in the overwhelming majority of retrospective-observational trials, RCTs, and meta-analyses in hospitalized COVID-19 patients. HC/CQ should not be prescribed for hospitalized COVID-19 patients outside of clinical trials.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

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 Effect of Nursing Guidelines on Coping of Infertile Couples Undergoing In Vitro Fertilization

2020 ◽  
Vol 2 (2) ◽  
pp. 11
Author(s):  
Gehan S. Abdelgelel ◽  
Shadia H. Muhsib ◽  
Mona H. Abdelaal ◽  
Randa M. Ibrahim
Keyword(s):  
In Vitro Fertilization ◽  
Coping Strategies ◽  
Unprotected Sex ◽  
The Body ◽  
University Hospital ◽  
Vitro Fertilization ◽  
Significant Difference ◽  
Infertile Couples ◽  
Nursing Guidelines

Context: Infertility is defined as not being able to conceive after one year of unprotected sex. In vitro fertilization (IVF) is a process of fertilization where an ovum is combined with sperm outside the body, in vitro. In vitro fertilization (IVF) is psychologically and emotionally stressful. Coping strategies are needed to master, tolerate, reduce, or minimize stressful events. Aim: This study aimed to evaluate the effect of nursing guidelines on coping of infertile couples' undergoing In Vitro Fertilization. Methods: A quasi-experimental research design was utilized to achieve the aim of this study. This study conducted at the assisted reproductive technology unit of Ain shams Maternity University Hospital on a convenient sample of 98 couples undergoing fertility treatments. Two tools were used for data collection; the first tool was a structured interviewing questionnaire to assess the couple's socio-demographic data, obstetric history, the couple's knowledge regarding in vitro fertilization. The second tool was ways of coping scale (WQS) to assess coping strategies among the infertile couple. Results: There is no statistically significant difference between couples in both groups according to their knowledge and their coping strategies to IVF before the implementation of nursing guidelines (p> 0.05). In contrast, there is a highly statistically significant improvement in knowledge and coping strategies of couples on the study group compared to control group couples after implementation of nursing guidelines(p<0.001). Conclusion: The finding of the current study supported the hypothesis, which stated that the infertile couples who will expose to the nursing guidelines, will exhibit improved coping strategies to IVF compared to the controls. The study recommended the application of nursing guidelines at the IVF unit of Ain Shams Maternity University Hospital and other settings for IVF treatment as routine care to improve infertile couples' coping strategies.

scholarly journals Peptide hormone relaxin: from molecular effects to clinical results

2021 ◽  
Vol 20 (1) ◽  
pp. 89-96
Author(s):  
O. V. Prokhorova ◽  
A. A. Olina ◽  
G. Kh. Tolibova ◽  
T. G. Tral
Keyword(s):  
Extracellular Matrix ◽  
Current System ◽  
Peptide Hormone ◽  
Clinical Results ◽  
Scientific Publications ◽  
Vitro Fertilization ◽  
Extracellular Matrix Components ◽  
Clinically Significant ◽  
Remodeling Of Extracellular Matrix

Introduction. The peptide hormone relaxin, which is produced by cells of the corpus luteum during and outside pregnancy, has a huge number of clinically significant effects, mediating many biological mechanisms, including antifibrotic, vasodilatory, angiogenic, anti-inflammatory and antiapoptotic effects.Purpose of the study: based on the study of modern literature data, to analyze the results of scientific research, representing the current system of views on the physiological and pathophysilogical effects of relaxin.Materials and methods. A study f scientific publications for the period from 2005 to 2020 in e PubMed and Elibrary databases was carried out using the keywords: relaxin, pregnancy, relaxin signaling pathway, reproductive system, extracellular matrix.Results and Discussion. The study of modern views on the physiology of relaxin has shown that this hormone mediates its effects by binding to the specific receptor RXFP1, which is localized in a large number of reproductive nonproductive tissues. Relaxin performs many functions related to the remodeling of the extracellular matrix and vasculature. The main uterotropic effects of this peptide include stimulation of growth and vascularization of the uterus, remodeling of extracellular matrix components, and regulation of vascular endothelial growth factor in preparation for implantation.Conclusion. The progress of the last decade in understanding the biochemistry of the hormone relaxin has formed the basis for a deeper penetration into all the variety of its physiological roles. The participation of relaxin in the mechanisms of relaxation of the myometrium during pregnancy, remodeling of the connective tissue of target organs in the antenatal period creases its potential clinical significance. The prospect of a possible therapeutic use of relaxin preparations in stimulating antenatal transformation of the cervix, in vitro fertilization, therapy of preeclampsia, acute heart failure and myocardial ischemia turns it into a potential therapeutic agent for these pathological conditions.

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 Mesenchymal stromal cells: a novel therapy for the treatment of chronic obstructive pulmonary disease?

Thorax ◽  
2018 ◽  
Vol 73 (6) ◽  
pp. 565-574 ◽  
Author(s):  
Winifred Broekman ◽  
Padmini P S J Khedoe ◽  
Koen Schepers ◽  
Helene Roelofs ◽  
Jan Stolk ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Animal Studies ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Novel Therapy ◽  
Model Studies

COPD is characterised by tissue destruction and inflammation. Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant. In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair. These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD. Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD. However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD. In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research.

Challenges on the effect of cell phone radiation on mammalian embryos and fetuses: a review of the literature

Zygote ◽  
2021 ◽  
pp. 1-7
Author(s):  
Maryam Mahaldashtian ◽  
Mohammad Ali Khalili ◽  
Fatemeh Anbari ◽  
Mohammad Seify ◽  
Manuel Belli
Keyword(s):  
Embryo Development ◽  
Animal Studies ◽  
Cell Phones ◽  
Cellular Phone ◽  
The Body ◽  
Human Embryos ◽  
Success Rates ◽  
Wide Range

Summary Cell phones operate with a wide range of frequency bands and emit radiofrequency-electromagnetic radiation (RF-EMR). Concern on the possible health hazards of RF-EMR has been growing in many countries because these RF-EMR pulses may be absorbed into the body cells, directly affecting them. There are some in vitro and in vivo animal studies related to the consequences of RF-EMR exposure from cell phones on embryo development and offspring. In addition, some studies have revealed that RF-EMR from cellular phone may lead to decrease in the rates of fertilization and embryo development, as well as the risk of the developmental anomalies, other studies have reported that it does not interfere with in vitro fertilization or intracytoplasmic sperm injection success rates, or the chromosomal aberration rate. Of course, it is unethical to study the effect of waves generated from cell phones on the forming human embryos. Conversely, other mammals have many similarities to humans in terms of anatomy, physiology and genetics. Therefore, in this review we focused on the existing literature evaluating the potential effects of RF-EMR on mammalian embryonic and fetal development.

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