scholarly journals A systematic review about animal models in homeopathic research: the last five years of PubMed indexed papers

2021 ◽  
Vol 14 (2) ◽  
pp. 45-45
Author(s):  
Leoni Villano Bonamin ◽  
Thayna Neves Cardoso ◽  
Aloisio Cunha Carvalho ◽  
Juliana G Amaral
Keyword(s):  
Animal Models ◽  
Ex Vivo ◽  
Biological Effects ◽  
High Dilution ◽  
Negative Results ◽  
Pubmed Database ◽  
High Dilutions

Background: This review is part of a special issue of Journal “Homeopathy” (ELSEVIER) to be published in 2015, about the follow-up of researches published in the book titled “Ultra-High Dilution, Physiology and Physics”, written in 1994 and edited by PC Endler and J Schulte. In 2010 a critical and conceptual review about animal models in homeopathy and high dilution research was published by our group. Thus, the aim of this study is to know how models and conclusions have progressed in this field in the last five years. Animal models represent one of the most illustrative examples of the biological effects of homeopathy and high dilutions. The main contribution of these studies is the comprehension of biological features and the phenomenology towards the high dilutions effects upon living systems, which represents an important step to the understanding of mechanisms of action of homeopathic medicines. Methods: 53 articles indexed in the PubMed database were systematically evaluated, in which 12 different animal species were used. 29 out of 53 reported studies were performed with “ultra-high” dilutions, whereas 14 studies were performed using dilutions in the range or below 10-23 or with commercial complexes (10). Results: Only 02 negative results were reported, both using commercial complexes as tested medicine (one each in fish and bee model). Since 2010, the quality of employed methods, mainly statistics, has improved. The inclusion of more refined protocols, such as in vitro primary cell cultures and ex vivo protocols (10/53), often with three or more repetitions, could be observed. These new methods allowed to observe epigenetic mechanisms involved. Conclusion: The demonstration of biological effects of homeopathy on animal models, in the past 5 years, is more refined than those previously described, helping in the development of paths to the mechanism of action discovery.

scholarly journals First-in-Human Mitochondrial Augmentation of Hematopoietic Stem Cells in Pearson Syndrome

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1024-1024 ◽  
Author(s):  
Elad Jacoby ◽  
Moriya Blumkin ◽  
Yair Anikster ◽  
Nira Varda-Bloom ◽  
Julia Pansheen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cellular Therapy ◽  
Ex Vivo ◽  
O2 Consumption ◽  
Atp Content ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Abstract Background: Pearson Syndrome (PS) is an ultra-rare disease caused by de-novo mitochondrial DNA (mtDNA) deletions. Patients present at infancy with sideroblastic anemia and later develop a multisystem metabolic disorder, leading to death in early or late childhood. No disease-modifying treatments are available for PS. Ex-vivo enrichment of functional mitochondria into various cells has been previously demonstrated, as has inter-cellular mitochondrial transfer. In preclinical models of mitochondrial and lysosomal disorders, hematopoietic stem and progenitor cells (HSCs) have been shown capable of carrying and transferring normal organelles into diseased tissues, thereby altering disease phenotype. Here, we show enrichment of PS-derived HSCs with wild-type mitochondria, a process termed mitochondrial augmentation. We further report on three patients with PS treated with autologous HSCs following ex-vivo mitochondrial augmentation. Methods: Diagnosis of PS was confirmed by MLPA and deletion-specific dPCR. Colony formation assays were performed on PS patient-derived HSCs, prior to and after mitochondrial augmentation. HSC mobilization was performed with GCSF alone (n=1) or with plerixafor (n=2) prior to leukapheresis. Autologous CD34+ cells were positively-selected using a CliniMACS system, followed by ex-vivo mitochondrial augmentation of the cells with maternal cryopreserved mitochondria carrying normal mtDNA as confirmed by MLPA. Enriched cells were intravenously infused without conditioning. Level of heteroplasmy (relative normal to deleted mtDNA) was determined by deletion-specific dPCR of DNA from peripheral blood. Patients were followed for a period of up to 1 year including clinical and metabolic evaluations. Adverse events were reported as per CTCAE v4.03. Cellular mitochondrial function was studied on peripheral blood mononuclear cells (PBMCs) by ATP content, O2 consumption and flow cytometry for TMRE (tetramethylrhodamine ethyl ester) and MTG (mitotracker green). Results: Three patients were treated with production and safety data available, and in two patients efficacy data is available. PS-patient derived HSCs have a diminished capacity to form colonies in vitro (median, 360 colonies per 5x104 cells vs. 1090 in healthy donors). HSC colony forming capacity increased by an average of 30% after mitochondrial augmentation. Target cell dose (4x106 CD34+ cells/kg) was not reached despite two leukapheresis procedures in patients 1 and 2, who received 1.1 and 1.8 million CD34+ cells/kg recipient, respectively. Patient 3 received 2.8 million cells/kg following a single apheresis. Mitochondrial enrichment in the products was 156%, 162% and 114% for patients 1, 2 and 3. To date, the only treatment-related adverse events noted were leukapheresis related, including anemia, hypocalcemia and alkalosis. In two patients with more than 3 months follow-up, we observed in vivo mitochondrial enrichment starting 3-4 months after cellular therapy, and throughout the follow-up period (Figure). Metabolic function of PBMCs showed improvement at 5 months post-treatment in lymphocyte ATP content, O2 consumption and TMRE:MTG ratio, indicating improved mitochondrial respiratory capacity. Improvement in mitochondrial heteroplasmy and function was in line with clinical findings. Following cell therapy, no events of metabolic crisis occurred, along with normalization of a pre-treatment negative base excess in patient 1 and ongoing improvement in baseline lactate levels in patient 2. Aerobic ability and fine motor functions were superior compared to baseline in both patients. Importantly, quality of life, as measured by the International Pediatric Mitochondrial Disease Score (IPMDS), was greatly improved after treatment. Conclusion: We report a first in human study with a novel form of cellular therapy, mitochondrial augmentation, in which we enrich HSCs with organelles encoding non-mutated version of the mtDNA sequence. We show the ability of mitochondrial augmentation to improve in vitro PS-derived HSC function, and improvement in metabolic determinants, aerobic capacity and quality of life of two patients treated. Together, these preliminary clinical data suggest that mitochondrial augmentation therapy is safe, and may alter the clinical course for patients with mitochondrial deletions/mutations including PS. Figure Figure. Disclosures Jacoby: Novartis Israel: Consultancy. Blumkin:Minovia Therapeutics: Employment. Sher:Minovia Therapeutics: Employment. Yivgi Ohana:Minovia Therapeutics: Employment. Toren:Novartis Israel: Consultancy.

Mannosylated Solid Lipid Nanocarriers Of Chrysin To Target Gastric Cancer: Optimization and Cell line Study.

2021 ◽  
Vol 18 ◽  
Author(s):  
Sonia S. Pandey ◽  
Farhinbanu I. Shaikh ◽  
Arti R. Gupta ◽  
Rutvi J. Vaidya
Keyword(s):  
Gastric Cancer ◽  
Particle Size ◽  
Ex Vivo ◽  
Biological Effects ◽  
Entrapment Efficiency ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Solid Lipid ◽  
Lipid Nanocarriers

Background: Despite significant biological effects, the clinical use of chrysin has been restricted because of its poor oral bioavailability. Objective: The purpose of the present research was to investigate the targeting potential of Mannose decorated chrysin (5,7- dihydroxyflavone) loaded solid lipid nanocarrier (MC-SLNs) for gastric cancer. Methods: The Chrysin loaded SLNs (C-SLNs) were developed optimized, characterized and further mannosylated. The C-SLNs were developed with high shear homogenizer, optimized with 32 full factorial designs and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Scanning Electron Microscope (SEM) and evaluated for particle size/polydispersity index, zeta-potential, entrapment efficiency, % release and haemolytic toxicity. The ex-vivo cytotoxicity study was performed on gastric cancer (ACG) and normal cell lines. Results: DSC and XRD data predict the chrysin encapsulation in lipid core and FTIR results confirm the mannosylation of C-SLNs. The optimized C-SLNs exhibited a narrow size distribution with a particle size of 285.65 nm. The % Entrapment Efficiency (%EE) and % controlled release were found to be 74.43% and 64.83%. Once C-SLNs were coated with mannose, profound change was observed in dependent variable - increase in the particle size of MC-SLNs (307.1 nm) was observed with 62.87% release and 70.8% entrapment efficiency. Further, the in vitro studies depicted MC- SLNs to be least hemolytic than pure chrysin and C-SLNs. MC-SLNs were most cytotoxic and were preferably taken up ACG tumor cells as evaluated against C-SLNs. Conclusion: These data suggested that the MC-SLNs demonstrated better biocompatibility and targeting efficiency to treat the gastric cancer.

Imaging ex vivo and in vitro brain morphology in animal models with ultrahigh resolution optical coherence tomography

2004 ◽  
Vol 9 (4) ◽  
pp. 719 ◽  
Author(s):  
Kostadinka Bizheva ◽  
Angelika Unterhuber ◽  
Boris Hermann ◽  
Boris Považay ◽  
Harald Sattmann ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Animal Models ◽  
Ex Vivo ◽  
Brain Morphology ◽  
Optical Coherence ◽  
Ultrahigh Resolution

scholarly journals An Ex Vivo Vessel Injury Model to Study Remodeling

2018 ◽  
Vol 27 (9) ◽  
pp. 1375-1389 ◽  
Author(s):  
Mehmet H. Kural ◽  
Guohao Dai ◽  
Laura E. Niklason ◽  
Liqiong Gui
Keyword(s):  
Shear Stress ◽  
Animal Models ◽  
Intimal Hyperplasia ◽  
Vascular Remodeling ◽  
Ex Vivo ◽  
Vessel Injury ◽  
Injury Model ◽  
Human Arteries

Objective: Invasive coronary interventions can fail due to intimal hyperplasia and restenosis. Endothelial cell (EC) seeding to the vessel lumen, accelerating re-endothelialization, or local release of mTOR pathway inhibitors have helped reduce intimal hyperplasia after vessel injury. While animal models are powerful tools, they are complex and expensive, and not always reflective of human physiology. Therefore, we developed an in vitro 3D vascular model validating previous in vivo animal models and utilizing isolated human arteries to study vascular remodeling after injury. Approach: We utilized a bioreactor that enables the control of intramural pressure and shear stress in vessel conduits to investigate the vascular response in both rat and human arteries to intraluminal injury. Results: Culturing rat aorta segments in vitro, we show that vigorous removal of luminal ECs results in vessel injury, causing medial proliferation by Day-4 and neointima formation, with the observation of SCA1+ cells (stem cell antigen-1) in the intima by Day-7, in the absence of flow. Conversely, when endothelial-denuded rat aortae and human umbilical arteries were subjected to arterial shear stress, pre-seeding with human umbilical ECs decreased the number and proliferation of smooth muscle cell (SMC) significantly in the media of both rat and human vessels. Conclusion: Our bioreactor system provides a novel platform for correlating ex vivo findings with vascular outcomes in vivo. The present in vitro human arterial injury model can be helpful in the study of EC-SMC interactions and vascular remodeling, by allowing for the separation of mechanical, cellular, and soluble factors.

Fludarabine, Cyclophosphamide and Rituximab in Waldenström’s Macroglobulinemia: An Effective Regimen Requiring a New Category of Response Criteria and a Delayed Assessment of Results

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1290-1290 ◽  
Author(s):  
Alessandra Tedeschi ◽  
Sara Miqueleiz ◽  
Francesca Ricci ◽  
Annalisa Luraschi ◽  
Mario Schiavone ◽  
...  
Keyword(s):  
Serum Albumin ◽  
International Workshop ◽  
Chemotherapeutic Agents ◽  
Hcv Rna ◽  
Delayed Response ◽  
Cell Transplant ◽  
Cutaneous Rash

Abstract Rituximab (R) is an active and well tolerated agent in the treatment of Waldenstrom’s Macroglobulinemia (WM) whether used in untreated or in refractory/relapsed pts. Furthermore, there is evidence that the association of R with chemotherapy may improve the quality of responses. Fludarabine and Cyclophosphamide (FC) are synergistic with R in vitro in lymphoma cell lines, and the administration of the three drugs is associated with higher response rates in other lymphoprolipherative disorders. We updated our experience to define the efficacy and tolerability of FCR in symptomatic pts with WM. Patients: Nineteen pts, median age 57 y, received R 375 mg/sqm iv d 1, F 25 mg/sqm iv d 2–4, C 250 mg/sqm iv d 2–4 every 4 weeks. Anti-infective prophylaxis with cotrimoxazole and acyclovir was administered. Median time from diagnosis to FCR treatment was 46 m (range 1–156). Five pts received FCR as first line treatment while 14 pts, of whom 8 refractory, had been previously treated with a median of 2 lines of therapy (range 1–6), 5 having previous received monoclonal antibodies. Splenomegaly and lymphadenopathy were present in 32% and 36% of pts, respectively. In 42% of cases Hb was <10g/dL, in 32% serum albumin was <3,5 g/dL, and in 53% β2M >3mg/dL. IgM median level was 4015 mg/dL (range 277– 10900), being > 4000 mg/dL in 53% of pts. Three pts were HCV-RNA positive and presented with cryoglobulinemia. Results: Pts received a median of 6 courses (range 3–6). Responses according to the IInd International Workshop on WM, updated in 2006, were categorized as follows: 15 PR (79%), 3 SD (16%), 1 PD (5%). Eight of the 15 PR pts could be considered as in “near CR”. In fact, the new response category could be justified by the achievement of complete resolution of symptoms, of adenopathy/organomegaly on CT scan, absence of malignant cells at BM immunophenotype and hystology, with only a persistence of a positive serum immunofixation (median serum MC protein of 0.3 g/dL). None of the variables considered (splenomegaly, lymphadenopathy, Hb level, serum albumin, β2M, IgM) was significantly associated with response. Ten pts showed a delayed response: 1 converted to CR after 4 m, in 9 a progressive reduction of MC is still detectable after a median follow-up of 10 m (range 4–31). Two pts underwent stem cell transplant (1 auto, 1 allo). Toxicity: Mild or moderate effects limited to the first and second R infusion, such as fever, hypotension, cutaneous rash, were seen in 5 pts (26%). None developed IgM “flare”. Neutropenia, observed in 82% of courses, was the main source of adverse effects. Two episodes of FUO and 1 clinically documented pneumonia were recorded. One pt died 3 m after the end of treatment while in PR for disseminated Aspegillosis. Conclusion: FCR regimen proved to be active and well tolerated even in previously heavily pre-treated WM pts; the response rate obtained is in line with clinical trials using R associated with other chemotherapeutic agents. A high percentage of near CRs and a progressive improvement of the quality of response has been observed even in pts with longer follow-up. The high incidence and long lasting episodes of neutropenia did not translate in major infectious episodes.

Ex vivo [11C]-(+)-PHNO binding is unchanged in animal models displaying increased high-affinity states of the D2receptor in vitro

Synapse ◽  
2009 ◽  
Vol 63 (11) ◽  
pp. 998-1009 ◽  
Author(s):  
Patrick N. McCormick ◽  
Shitij Kapur ◽  
Greg Reckless ◽  
Alan A. Wilson
Keyword(s):  
Animal Models ◽  
Ex Vivo ◽  
High Affinity

scholarly journals In vitroandex vivomeasurement of the biophysical properties of blood using microfluidic platforms and animal models

The Analyst ◽  
2018 ◽  
Vol 143 (12) ◽  
pp. 2723-2749 ◽  
Author(s):  
Yang Jun Kang ◽  
Sang-Joon Lee
Keyword(s):  
Animal Models ◽  
Ex Vivo ◽  
Biophysical Properties ◽  
Microfluidic Platforms

Several techniques for thein vitroandex vivomeasurement of hemorheological properties using microfluidic platforms and animal models were reviewed.

scholarly journals False Covid-19 Test Results – Could We Do Things Better? A Personal Opinion

2020 ◽  
Vol 8 (5) ◽  
Author(s):  
Suzanne Lisbeth Ekelund
Keyword(s):  
False Positive ◽  
False Negative ◽  
Test Results ◽  
Negative Results ◽  
False Negative Results ◽  
Personal Opinion ◽  
Potential Problems

This paper describes the problems with false covid-19 test results, both false positive and false negative results. The problems are related to the quality of tests, test sampling and the currently limited follow-up procedures. A test and follow-up strategy that could decrease the potential problems is suggested.

scholarly journals Immunological research about ultra-high dilution and Homeopathy: From 1994 to 2014

2021 ◽  
Vol 14 (2) ◽  
pp. 46-46
Author(s):  
Leoni Villano Bonamin
Keyword(s):  
In Vitro Models ◽  
Experimental Models ◽  
Parasitic Infections ◽  
Special Focus ◽  
High Dilution ◽  
Multi Centre Study ◽  
High Dilutions ◽  
Immunological Research ◽  
Dilution Effects

Background: This review is part of a special issue of journal “Homeopathy” (ELSEVIER) scheduled for publication in 2015, about the follow-up of researches published in the book titled “Ultra-High Dilution, Physiology and Physics”, written and edited by PC Endler and J Schulte in 1994. In this book, Prof. Madeleine Bastide described experimental models in immunology that were used during the 1980s to investigate high dilution effects on several biological systems. Bastide categorized available papers in four categories: high dilutions of antigens; high dilutions of thymus, bursa and other hormones; high dilutions of cytokines and immunopharmacological activity of silica. The studies about high dilutions of antigens were interrupted from this time onwards. Only the in vitro models developed on antigens and histamine dilutions lasted up to 2009. During this process, a huge multi-centre study was performed, with high reproducibility, and involving different independent laboratories. The studies about highly diluted cytokines, thymulin and other hormones brought some regulatory properties of endogenous substances prepared homeopathically, with special focus on epigenetic mechanisms of highly diluted cytokines. The frequently studied substance was Thymulin 5cH, which improved the activity of phagocytes in viral, bacterial and parasitic infections. Studies about the immunopharmacological activity of silica have assumed a new focus: the putative role of silica as active contaminant present in high dilutions, that is still under discussion.

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