scholarly journals Use of Saline as a Placebo in Intra-articular Injections in Osteoarthritis: Potential Contributions to Nociceptive Pain Relief

2017 ◽  
Vol 11 (1) ◽  
pp. 16-22 ◽  
Author(s):  
David Bar-Or ◽  
Leonard T. Rael ◽  
Edward N. Brody
Keyword(s):  
Clinical Trials ◽  
Literature Search ◽  
Platelet Rich Plasma ◽  
Sodium Hyaluronate ◽  
Physiological Saline ◽  
Weight Fraction ◽  
Solute Concentration ◽  
Osteoarthritis Of The Knee ◽  
Therapeutic Effects ◽  
Limited Mobility

Background: Osteoarthritis of the knee (OAK) is a severe debilitating condition characterized by joint pain, stiffness, and resultant limited mobility. In recent years, intra-articular (IA) injections have been used to relieve symptoms and have succeeded to varying degrees either with sodium hyaluronate preparations or with a biologic. Objective: The objective of this review is to evaluate multiple studies that demonstrate some relief from the symptoms of OAK in the saline arm of various clinical trials. Method: A thorough literature search (PubMed) was performed assessing the pain efficacy of various compounds compared to saline injections in clinical trials. A total of 73 studies were identified in the literature search including a total of 5,816 patients. These clinical trials all involved the IA injection of a viscosupplement (hyaluronate, platelet rich plasma (PRP), etc.) or a biologic (the low molecular weight fraction (< 5kDa) of human serum albumin (LMWF-5A)). For all of these studies, the control arm was injection of sterile physiological saline that approximates the salt concentration and total solute concentration of blood and most tissues. Results: Based on our review of the current literature, the tested compounds performed with mixed results when compared to saline injections. Moreover, OAK is a variable disease, with severity measured on the Kellgren and Lawrence (KL) scale where various hyaluronate preparations have a therapeutic effect mostly on KL 2-3 patients while a biologic works best on KL 3-4 patients. Conclusion: Since the effect of saline injection is always greater than no treatment, the evaluations of these treatments can be confounded in clinical trials. Therefore, the question of whether there are known therapeutic effects of saline injections might explain these results.

scholarly journals Methods of drug therapy for severe dry eye disease

2021 ◽  
Vol 18 (1) ◽  
pp. 109-116
Author(s):  
G. R. Semak
Keyword(s):  
Clinical Trials ◽  
Drug Therapy ◽  
Dry Eye ◽  
Ocular Surface ◽  
High Efficiency ◽  
Platelet Rich Plasma ◽  
Sodium Hyaluronate ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Pubmed Database

Treatment of chronic dystrophic diseases of the ocular surface always requires concomitant correction of severe dry eye disease (DED). The purpose of this publication was to analyze the literature data illustrating the current trends in the development of drug therapy for severe dry eye disease of non-Shegren’s etiology.The search for thematic publications was carried out in the PubMed database. The query “(dry-eye-disease AND treatment) NOT Sjögren” (filter: clinical trials, randomized controlled clinical trials, meta-analyzes) found 56 results since 2019.The review included 11 publications describing the results of clinical studies of the effectiveness of drug methods in the treatment of severe DED.In the treatment of severe DED, the prevailing direction of research is the relief of inflammation in the ocular surface tissues. Among the non-steroidal immunomodulatory drugs, the majority of studies were dedicated to cyclosporine, including its nanoemulsion form, diquafosol and bevacizumab. Their effectiveness and safety have been proven. In the Republic of Belarus, there is no unified approach to the management of patients with severe and comorbid DED. The main focus is on the activation of regenerative processes. Platelet rich plasma and subconjunctival administration of low molecular weight sodium hyaluronate demonstrated high efficiency.

Preparation of a Viable Population of Indium-111- Labelled Human Blood Platelets

1979 ◽  
Vol 42 (05) ◽  
pp. 1473-1482 ◽  
Author(s):  
A Dup Heyns ◽  
P N Badenhorst ◽  
H Pieters ◽  
M G Lötter ◽  
P C Minnaar ◽  
...  
Keyword(s):  
Platelet Rich Plasma ◽  
Blood Platelets ◽  
Kinetic Studies ◽  
Physiological Saline ◽  
Human Platelets ◽  
Autologous Plasma ◽  
Platelet Suspension ◽  
Viable Population ◽  
Indium 111

SummaryFactors influencing labelling of human platelets with 111Indium-8-hydroxyquinoline ([111In]-oxine) in a physiological saline medium were investigated. The efficiency of labelling is influenced by time of incubation, concentration of oxine, and pH of the incubating medium. It was found that a viable platelet population could be labelled under the following conditions: (1) centrifugation of platelet rich plasma in polystyrene conical tubes at 800 g for 15 min; (2) resuspension of the platelet pellet in saline, pH 5.5; (3) incubating for 30 min at 22°C with [111In]-oxine at a concentration of 6.25 mg oxine/litre platelet suspension; (4) washing once with platelet poor autologous plasma (PPP); and (5) finally resuspending the platelets in PPP. The labelled platelets aggregated normally with collagen and ADP. Electron microscopy, done immediately after labelling, showed internal organelle reorganization characteristic of activated platelets. These ultrastructural features were reversible on incubation in PPP at 37°C for 30 min. The 111In is not released from aggregated platelets and the label does not elute from incubated platelets for at least five hr. We conclude that human platelets thus labelled are suitable for in vivo kinetic studies.

The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for Their Use as an Add-on Therapy in Schizophrenia

2020 ◽  
Vol 26 ◽  
Author(s):  
Felix-Martin Werner ◽  
Rafael Coveñas
Keyword(s):  
Clinical Trials ◽  
Maintenance Therapy ◽  
Antipsychotic Drug ◽  
Cognitive Functions ◽  
Antipsychotic Drugs ◽  
Psychotic Disorders ◽  
Therapeutic Effects ◽  
Treatment Resistant ◽  
Long Acting ◽  
Novel Antipsychotic

Background: Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders and, in this case, they can be treated with clozapine. In these patients and based on previous reviews on novel antipsychotic drugs, it is important to know whether an add-on therapy with new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. Objective: The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of current available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. Results: The mechanisms of action, the therapeutic effects and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole and lumateperone are up-dated. Published case reports of patients with treatmentresistant psychoses are also discussed. These patients were treated with clozapine but a high PANSS total score was observed. Only an add-on therapy with cariprazine improved the score and, above all, negative schizophrenic symptoms and cognitive functions. To ensure a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs may be a choice for a maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, are being investigated in preclinical and clinical trials. Conclusion: In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether a combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are a safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by an add-on therapy with cognition enhancing drugs.

Current RNA-based Therapeutics in Clinical Trials

2019 ◽  
Vol 19 (3) ◽  
pp. 172-196 ◽  
Author(s):  
Ling-Yan Zhou ◽  
Zhou Qin ◽  
Yang-Hui Zhu ◽  
Zhi-Yao He ◽  
Ting Xu
Keyword(s):  
Clinical Trials ◽  
Rapid Development ◽  
Genetic Diseases ◽  
Three Dimensional ◽  
Therapeutic Effects ◽  
Messenger Rnas ◽  
Small Interfering Rnas ◽  
Rna Modifications ◽  
Guide Rna ◽  
Endogenous Genes

Long-term research on various types of RNAs has led to further understanding of diverse mechanisms, which eventually resulted in the rapid development of RNA-based therapeutics as powerful tools in clinical disease treatment. Some of the developing RNA drugs obey the antisense mechanisms including antisense oligonucleotides, small interfering RNAs, microRNAs, small activating RNAs, and ribozymes. These types of RNAs could be utilized to inhibit/activate gene expression or change splicing to provide functional proteins. In the meantime, some others based on different mechanisms like modified messenger RNAs could replace the dysfunctional endogenous genes to manage some genetic diseases, and aptamers with special three-dimensional structures could bind to specific targets in a high-affinity manner. In addition, the recent most popular CRISPR-Cas technology, consisting of a crucial single guide RNA, could edit DNA directly to generate therapeutic effects. The desired results from recent clinical trials indicated the great potential of RNA-based drugs in the treatment of various diseases, but further studies on improving delivery materials and RNA modifications are required for the novel RNA-based drugs to translate to the clinic. This review focused on the advances and clinical studies of current RNA-based therapeutics, analyzed their challenges and prospects.

scholarly journals Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2506
Author(s):  
Wamidh H. Talib ◽  
Ahmad Riyad Alsayed ◽  
Alaa Abuawad ◽  
Safa Daoud ◽  
Asma Ismail Mahmod
Keyword(s):  
Clinical Trials ◽  
Current Knowledge ◽  
Biological Activities ◽  
Experimental Studies ◽  
Therapeutic Effects ◽  
Cell Proliferation Inhibition ◽  
Different Types ◽  
Solid Foundation

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

scholarly journals Recombinant Human Adenovirus-p53 Therapy for the Treatment of Oral Leukoplakia and Oral Squamous Cell Carcinoma: A Systematic Review

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 438
Author(s):  
Jagadish Hosmani ◽  
Shazia Mushtaq ◽  
Shahabe Saquib Abullais ◽  
Hussain Mohammed Almubarak ◽  
Khalil Assiri ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Oral Cancer ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Oral Leukoplakia ◽  
Research Articles ◽  
Original Research ◽  
Therapeutic Effects ◽  
The World

Background and Objectives: Oral cancer is the 6th most common cancer in the world and oral leukoplakia is an oral potentially malignant disorder that could develop into oral cancer. This systematic review focusses on randomized clinical trials for recombinant adenovirus p-53 (rAD-p53) therapy for the treatment of oral leukoplakia and cancer. Materials and Methods: We searched for research articles on various databases such as Pubmed/Medline, Embase, CNKI (China National Knowledge Infra-structure), Springerlink, cochrane and Web of sciences from 2003 to 2020. MeSH (Medical Subject Headings) terms were used for the search. Inclusion criteria included original research, randomized clinical trials and articles only in English language. Exclusion criteria were any articles that were not research articles, not randomized trials, non-human studies, etc. The articles were further graded on the Jadad scale. Results: 578 articles were assessed from various databases; only 3 articles were found to be appropriate for this review. Thus, meta-analysis was not performed because of heterogeneity and lack of data. In the three studies, whether rAD-p53 was used as a standalone therapy or with other therapies, there was a beneficial effect of the therapy. Furthermore, there were no serious adverse events and the only adverse events reported were fever, pain at the local injection site, flu-like symptoms and lowered WBC count. Conclusions: Thus, we can conclude that this therapy has a potential for beneficial therapeutic effects and further clinical trials with more patients need to be performed to get better understanding of the effect of rAD-p53 therapy, which probably will pave the way to its approval in other parts of the world.

scholarly journals AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Sipin Zhu ◽  
Yibo Ying ◽  
Jiahui Ye ◽  
Min Chen ◽  
Qiuji Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Control Group ◽  
Therapeutic Effects ◽  
Hypoxia Response Element ◽  
Neurofilament Protein ◽  
Response Element ◽  
Hypoxia Response ◽  
Cord Injury

AbstractNeural stem cell (NSCs) transplantation has been one of the hot topics in the repair of spinal cord injury (SCI). Fibroblast growth factor (FGF) is considered a promising nerve injury therapy after SCI. However, owing to a hostile hypoxia condition in SCI, there remains a challenging issue in implementing these tactics to repair SCI. In this report, we used adeno-associated virus 2 (AAV2), a prototype AAV used in clinical trials for human neuron disorders, basic FGF (bFGF) gene under the regulation of hypoxia response element (HRE) was constructed and transduced into NSCs to yield AAV2-5HRE-bFGF-NSCs. Our results showed that its treatment yielded temporally increased expression of bFGF in SCI, and improved scores of functional recovery after SCI compared to vehicle control (AAV2-5HRE-NSCs) based on the analyses of the inclined plane test, Basso–Beattie–Bresnahan (BBB) scale and footprint analysis. Mechanistic studies showed that AAV2-5HRE-bFGF-NSCs treatment increased the expression of neuron-specific neuronal nuclei protein (NeuN), neuromodulin GAP43, and neurofilament protein NF200 while decreased the expression of glial fibrillary acidic protein (GFAP) as compared to the control group. Further, the expressions of autophagy-associated proteins LC3-II and Beclin 1 were decreased, whereas the expression of P62 protein was increased in AAV2-5HRE-bFGF-NSCs treatment group. Taken together, our data indicate that AAV2-5HRE-bFGF-NSCs treatment improved the recovery of SCI rats, which is accompanied by evidence of nerve regeneration, and inhibition of SCI-induced glial scar formation and cell autophagy. Thus, this study represents a step forward towards the potential use of AAV2-5HRE-bFGF-NSCs for future clinical trials of SCI repair.

scholarly journals Effect of Platelet-Rich Plasma on M1/M2 Macrophage Polarization

2021 ◽  
Vol 22 (5) ◽  
pp. 2336
Author(s):  
Ryoka Uchiyama ◽  
Eriko Toyoda ◽  
Miki Maehara ◽  
Shiho Wasai ◽  
Haruka Omura ◽  
...  
Keyword(s):  
Culture Media ◽  
Platelet Rich Plasma ◽  
Point Of Care ◽  
Macrophage Polarization ◽  
Osteoarthritis Of The Knee ◽  
M2 Macrophage ◽  
Related Factors ◽  
Humoral Factors ◽  
M1 Macrophage ◽  
M2 Macrophage Polarization

Osteoarthritis of the knee (OAK) is a chronic degenerative disease and progresses with an imbalance of cytokines and macrophages in the joint. Studies regarding the use of platelet-rich plasma (PRP) as a point-of-care treatment for OAK have reported on its effect on tissue repair and suppression of inflammation but few have reported on its effect on macrophages and macrophage polarization. Based on our clinical experience with two types of PRP kits Cellaid Serum Collection Set P type kit (leukocyte-poor-PRP) and an Autologous Protein Solution kit (APS leukocyte-rich-PRP), we investigated the concentrations of humoral factors in PRPs prepared from the two kits and the effect of humoral factors on macrophage phenotypes. We found that the concentrations of cell components and humoral factors differed between PRPs purified using the two kits; APS had a higher concentration of M1 and M2 macrophage related factors. The addition of PRP supernatants to the culture media of monocyte-derived macrophages and M1 polarized macrophages revealed that PRPs suppressed M1 macrophage polarization and promoted M2 macrophage polarization. This research is the first to report the effect of PRPs purified using commercial kits on macrophage polarization.

Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction

Cardiology ◽  
2016 ◽  
Vol 135 (4) ◽  
pp. 221-227 ◽  
Author(s):  
Shao-Ling Yang ◽  
Ke-Qiang Tang ◽  
Jun-Jia Tao ◽  
Ai-Hong Wan ◽  
Yan-Duan Lin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Function ◽  
Rabbit Model ◽  
Physiological Saline ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Therapeutic Effects ◽  
Ventricular Ejection Fraction ◽  
Cluster Of Differentiation

Objectives: We aimed to evaluate whether ultrasound (US) and microbubble-mediated delivery of Cluster of Differentiation 151 (CD151) could enhance the therapeutic effects of CD151 on myocardial infarction (MI). Methods: A rabbit model of MI was established by a modified Fujita method. Then, 50 MI rabbits were randomly divided into 5 groups, including G1 (CD151 plasmid and physiological saline in the presence of US); G2 (CD151 and Sonovue in the presence of US); G3 (CD151 and Sonovue in the absence of US); G4 (Sonovue in the absence of US), and a control group (physiological saline in the absence of US). After 14 days of treatment, the expression of CD151 was detected by Western blot. Besides, vessel density of peri-infarcted myocardium was measured by immunohistochemistry, and cardiac function was analyzed by echocardiography. Results: The rabbit model of MI was established successfully. CD151 injection increased the expression of CD151 and microvessel density in the myocardium of MI rabbits. Heart function was significantly improved by CD151, which exhibited increased left ventricular ejection fraction, left ventricular fractional shortening and a reduced Tei index. Besides, US Sonovue significantly increased the expression efficiency of CD151. Conclusion: US microbubble was an effective vector for CD151 delivery. CD151 might be an effective therapeutic target for MI.

Tamoxifen for Prevention of Breast Cancer

2003 ◽  
Vol 37 (2) ◽  
pp. 268-273 ◽  
Author(s):  
Robert J Cersosimo
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Literature Search ◽  
Data Sources ◽  
Data Synthesis ◽  
Increased Risk ◽  
Key Words Tamoxifen ◽  
Not At Risk ◽  
Prevention Of Breast Cancer ◽  
Common Malignancy

OBJECTIVE: To review data on the use of tamoxifen for primary prevention of breast cancer. DATA SOURCES: A literature search was performed through MEDLINE (1992–May 2002) using the key words tamoxifen, breast cancer, and prevention. DATA SYNTHESIS: Breast cancer is the most common malignancy detected in American women. Attempts to reduce morbidity and mortality include early detection programs and chemoprevention. Clinical trials of tamoxifen for reduction of breast cancer risk are reviewed. CONCLUSIONS: Tamoxifen may reduce the risk of primary breast cancer in women at increased risk. The benefit of tamoxifen in women who are not at risk is uncertain. The risks of developing thromboembolic disorders or endometrial cancer must be considered before tamoxifen is prescribed. Women should be given all of the information about the benefits and risks of tamoxifen use so that they can make an informed decision based on the best data available.

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