Inhibition of RNA Synthesis in vitro by Acridines - Relation between Structure and Activity

1998 ◽  
Vol 53 (5-6) ◽  
pp. 359-368 ◽  
Author(s):  
Mariola K. Piestrzeniewicz ◽  
Dorota Wilmańska ◽  
Kazimierz Studzian ◽  
Janusz Szemraj ◽  
Małgorzata Czyż ◽  
...  
Keyword(s):  
Biological Effect ◽  
Topoisomerase Ii ◽  
Rna Synthesis ◽  
Biological Effects ◽  
The Other ◽  
Inhibitory Potency ◽  
Enzyme Binding ◽  
Primary Mechanism ◽  
Structure And Activity

Abstract The effects of acridine derivatives (proflavine and 2,7-dialkyl derivatives, diacridines and triacridines, 9-aminoacridine carboxamides, and 9-anilinoacridine, amsacrine and its congeners) on overall RNA synthesis in vitro, on synthesis of initiating oligonucleotides and the binding of the enzyme to DNA were studied. The primary mechanism of action is related to inhibition of the enzyme binding to DNA. The acridines (intercalating or non-intercalating and bis-intercalating ligands) assayed here differ in the properties of their complexes with DNA. Correlation is generally observed between inhibition of RNA synthesis in vitro and cytotoxicity in cell cultures for di- and triacridines and 9-aminoacridine carboxamide derivatives. No relationship was found between the effect on RNA polymerase system and biological effects for amsacrine and its derivatives in contrast to the other series of acridines studied here. The aniline ring seems to decrease the inhibitory potency of a ligand. The discrepancy between the biological effect and RNA synthesis inhibition may be due to a different mechanism of cytotoxicity action of amsacrine which is a potent topoisomerase II poison.

Molecular Characterization of the t(15;17)(q22;21) in Epirubicin-Related Acute Promyelocytic Leukaemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 791-791
Author(s):  
Ashley Nicole Mays ◽  
Neil Osheroff ◽  
Carolyn Felix ◽  
Jo Ann Byl ◽  
Kandeepan Saravanamuttu ◽  
...  
Keyword(s):  
Long Range ◽  
Acute Promyelocytic Leukaemia ◽  
Topoisomerase Ii ◽  
The Other ◽  
Promyelocytic Leukaemia ◽  
Chromosome 15 ◽  
Accession Number ◽  
Long Range Pcr ◽  
Intron 2

Abstract Chromosomal translocations generating chimaeric oncoproteins play an important role in leukaemogenesis, but mechanisms underlying their formation are largely unclear. Substantial insights can be gained from the analysis of therapy-related acute myeloid leukaemias (t-AMLs), which are becoming an increasing healthcare problem as more patients survive their primary cancers. Exposure to agents targeting topoisomerase II (topoII) predisposes to the development of leukaemias with balanced translocations e.g. t(15;17), fusing PML and RARA genes, in therapy-related acute promyelocytic leukaemia (t-APL) which is particularly associated with prior treatment involving mitoxantrone or epirubicin. Using long-range PCR and sequencing to define genomic junction regions we found that in t-APL cases arising in breast cancer patients exposed to the former agent, chromosome 15 breakpoints clustered tightly in an 8 bp “hotspot” region in PML intron 6, which was shown by functional assay to be a preferred site of mitoxantrone-induced DNA topoII cleavage (Mistry et al, NEJM 2005). Subsequent analysis of an independent cohort of t-APL cases arising after mitoxantrone therapy for multiple sclerosis confirmed chromosome 15 breakpoint clustering in the “hotspot” and identified a recurrent breakpoint within RARA intron 2. This hotspot also was shown to be a preferential site of mitoxantrone-induced cleavage in vitro (Hasan et al, Blood 2008). However, the molecular basis of epirubicin-related APL remains uncertain. Therefore we used long-range PCR and sequence analysis to define translocation breakpoints in 6 patients who developed APL after treatment involving epirubicin-containing regimens for prior breast carcinoma. While mitoxantrone-related APL displayed a bias towards breakpoints occurring within PML intron 6 (bcr1), epirubicin-related breakpoints fell within intron 3 (n=2) or intron 6 (n=4) and were outside the mitoxantrone-related “hotspot” (located at position 1484 according to accession number S57791). Breakpoints within the RARA locus were distinct from those observed in mitoxantrone-related APL. Interestingly, the chromosome 15 or chromosome 17 breakpoints of 4 of the epirubicin-related t-APLs fell in close proximity (within 1–4bp) to one of the other cases. Two shared a breakpoint location in PML intron 6 that occurred at bases 1185 and 1186 (accession number S57791) and two fell within RARA intron 2 at base numbers 16193 and 16197 (accession number AJ297538). Given that PML intron 6 and RARA intron 2 are ~1kb and 17kb in length, respectively, such breakpoint clustering was unlikely to have occurred by chance and consistent with functional sites of topoII cleavage. In addition, in vitro DNA cleavage assays demonstrated that heat stable topoII cleavage complexes are formed at the exact location of the breakpoint identified in one of the other patients, at position 1969 in PML intron 6, which were enhanced by the presence of epirubicin. This study suggests that mitoxantrone and epirubicin exhibit preference differences in sites of DNA damage induced by topoisomerase II, which may underlie the propensity to develop specific molecularly-defined subtypes of t-AML according to the nature of the particular chemotherapeutic agent used.

scholarly journals Exosomes derived from human CD34+ stem cells transfected with miR-26a prevent glucocorticoid-induced osteonecrosis of the femoral head by promoting angiogenesis and osteogenesis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Rongtai Zuo ◽  
Lingchi Kong ◽  
Mengwei Wang ◽  
Wenbo Wang ◽  
Jia Xu ◽  
...  
Keyword(s):  
Femoral Head ◽  
Rat Model ◽  
Biological Effect ◽  
Umbilical Vein ◽  
Biological Effects ◽  
Endothelial Cell Migration ◽  
Osteogenic Potential ◽  
Alizarin Red ◽  
Tube Forming

Abstract Background Damaged endothelial cells and downregulated osteogenic ability are two key pathogenic mechanisms of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Recent studies suggested that transplantation of CD34+ stem cell-derived exosomes (CD34+-Exos) can treat ischemic diseases by promoting neovascularization and that miR-26a is an important positive regulator of osteogenesis. Moreover, the biological effect of exosomes is closely related to their cargo miRNAs. However, it is not clear whether increasing the abundance of miR-26a in CD34+-Exos will inhibit the progress of GC-induced ONFH. Methods MiR-26a was overexpressed in CD34+-Exos (miR-26a-CD34+-Exos) to increase their osteogenic potential. The angiogenic potential of miR-26a-CD34+-Exos was then examined through evaluations of migration and tube-forming capacities in vitro. In addition, in order to observe the osteogenic effect of miR-26a-CD34+-Exos on bone marrow stromal cells (BMSCs), Alizarin red staining, alkaline phosphatase (ALP) activity assays, and qPCR were carried out. Finally, miR-26a-CD34+-Exos were injected into a GC-induced ONFH rat model to prevent the progress of GC-induced ONFH. The biological effects of miR-26a-CD34+-Exos on the ONFH model were evaluated by micro-CT, angiography, and histological staining. Results Our data showed that miR-26a-CD34+-Exos enhanced human umbilical vein endothelial cell migration and tube-forming capacities. Furthermore, miR-26a-CD34+-Exos strengthened the osteogenic differentiation of BMSCs under the influence of GCs in vitro. Finally, the miR-26a-CD34+-Exos increased the vessel density and trabecular bone integrity of the femoral head in the GC-induced ONFH rat model, which inhibited the progress of ONFH. Conclusions MiR-26a-CD34+-Exos protect the femoral head from damage caused by GCs by strengthening angiogenesis and osteogenesis. The biological effect of miR-26a-CD34+-Exos make them suitable for application in the prevention of GC-induced ONFH.

scholarly journals Antiproliferative and Enzyme Docking Analysis of Engleromycin from Engleromyces goetzei

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 166 ◽  
Author(s):  
Yongli Zhang ◽  
Guilin Chen ◽  
Hong Ma ◽  
Mingquan Guo
Keyword(s):  
Antiproliferative Activity ◽  
Topoisomerase Ii ◽  
Antitumor Agents ◽  
Human Cancer ◽  
Biological Effects ◽  
A549 Cells ◽  
Human Cancer Cell Lines ◽  
Ic50 Values ◽  
Ht 29

Engleromyces goetzei P. Henn. (E. goetzei) has been widely used as a traditional herb for many years in Kenya due to its diverse biological effects. Although engleromycin was first isolated from E. goetzei in 1980, its pharmacological activity is still unknown. In this study, engleromycin from E. goetzei was identified by spectroscopic analyses, and subsequently examined for its antiproliferative activity using human cancer cell lines of SGC-7901, HT-29, HeLa and A549. As a result, it was revealed that engleromycin strongly inhibited the growth of SGC-7901, HT-29, HeLa and A549 cells with IC50 values at 26.77 ± 1.69 µM, 7.73 ± 0.18 µM, 7.00 ± 0.12 µM and 3.14 ± 0.03 µM, respectively. The results of topoisomerase II (Top II) inhibition assay in vitro implied that engleromycin might be a Top II inhibitor. Further insights into the potential mechanism of antiproliferative activity displayed that engleromycin could dock into the binding pockets of Top II, like the clinical inhibitor doxorubicin, and then inhibit the biological activity of Top II. Taken together, our findings suggest that engleromycin has an anticancer potential, and may serve as a leading compound for the development of antitumor agents.

scholarly journals Chromosome damage induced by DNA topoisomerase II inhibitors combined with g-radiation in vitro

1998 ◽  
Vol 21 (3) ◽  
pp. 407-417
Author(s):  
Maria Cristina P. Araújo ◽  
Francisca da Luz Dias ◽  
Andréa O. Cecchi ◽  
Lusânia M.G. Antunes ◽  
Catarina S. Takahashi
Keyword(s):  
Cho Cells ◽  
Topoisomerase Ii ◽  
Chinese Hamster ◽  
The Other ◽  
Additive Effects ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase ◽  
Topoisomerase Ii Inhibitors ◽  
Radiation Induced

Combined radiation and antineoplastic drug treatment have important applications in cancer therapy. In the present work, an evaluation was made of two known topoisomerase II inhibitors, doxorubicin (DXR) and mitoxantrone (MXN), with g-radiation. The effects of DXR or MXN on g-radiation-induced chromosome aberrations in Chinese hamster ovary (CHO) cells were analyzed. Two concentrations of each drug, 0.5 and 1.0 µg/ml DXR, and 0.02 and 0.04 µg/ml MXN, were applied in combination with two doses of g-radiation (20 and 40 cGy). A significant potentiating effect on chromosomal aberrations was observed in CHO cells exposed to 1.0 µg/ml DXR plus 40 cGy. In the other tests, the combination of g-radiation with DXR or MXN gave approximately additive effects. Reduced mitotic indices reflected higher toxicity of the drugs when combined with radiation.

scholarly journals In vitro Methods to Study Antioxidant and Some Biological Activities of Essential Oils: a Review

2021 ◽  
Vol 12 (3) ◽  
pp. 3332-3347
Keyword(s):  
Essential Oils ◽  
Biological Activities ◽  
Biological Effects ◽  
The Other ◽  
Present Review ◽  
In Vitro Methods ◽  
Potential Benefits ◽  
Experimental Protocols ◽  
The One

As essential oils (EOs) represent a new source of efficient and safe agents for health nowadays, the present review brings together the in vitro methods widely used to evaluate the antioxidant and some biological activities especially, antidiabetic, anticancer, antimicrobial, and anti-inflammatory activities of EOs, in order to valorize these EOs and to highlight their potential benefits. Moreover, each method cited is along with its aim, principle, advantages and limitations, experimental protocols, and notes. Hence, this review will help researchers working on EOs, to save time while accessing this summary document on the one hand, and on the other hand, it will contribute to scientific approval of in vitro antioxidant and biological effects of EOs for future useful purposes.

scholarly journals In vitro activity of HSR-903, a new quinolone.

1997 ◽  
Vol 41 (6) ◽  
pp. 1326-1330 ◽  
Author(s):  
Y Takahashi ◽  
N Masuda ◽  
M Otsuki ◽  
M Miki ◽  
T Nishino
Keyword(s):  
Topoisomerase Ii ◽  
Inoculum Size ◽  
The Other ◽  
Vitro Activity ◽  
Penicillin G ◽  
In Vitro Activity ◽  
Postantibiotic Effect ◽  
The Family ◽  
Acidic Conditions

The in vitro activity of the new fluoroquinolone HSR-903 was compared with those of ciprofloxacin, lomefloxacin, sparfloxacin, and levofloxacin. HSR-903 inhibited 90% of methicillin-susceptible and -resistant Staphylococcus aureus (MRSA) clinical isolates at 0.78 and 1.56 microg/ml, respectively, and its activity against MRSA was 16-fold higher than those of sparfloxacin and levofloxacin and 64-fold higher than that of ciprofloxacin. The MICs at which 90% of the isolates are inhibited (MIC90s) of HSR-903 for Streptococcus pyogenes and penicillin G-susceptible and -resistant Streptococcus pneumoniae (PRSP) were 0.10, 0.05, and 0.05 microg/ml, respectively. Against PRSP, the activity of HSR-903 was 4-fold higher than that of sparfloxacin and 32- to 256-fold higher than those of the other quinolones. The MIC90 of HSR-903 for Enterococcus faecalis was 0.20 microg/ml, and HSR-903 was more active than the other quinolones against enterococci. The activity of HSR-903 against members of the family Enterobacteriaceae and Pseudomonas aeruginosa was roughly similar to that of ciprofloxacin and greater than those of the other quinolones. Against Haemophilus influenzae, Moraxella catarrhalis, and Helicobacter pylori, HSR-903 was the most potent of the quinolones tested. The activity of HSR-903 was not affected by the medium, the inoculum size, or the addition of serum, but decreased under acidic conditions, as did those of the other quinolones tested. HSR-903 exhibited rapid bactericidal action and had a good postantibiotic effect on S. aureus and P. aeruginosa. HSR-903 inhibited supercoiling by DNA gyrase from Escherichia coli, but it was much less active against human topoisomerase II.

THE MODE OF ACTION OF ANTITHYROID DRUGS: RESULTS WITH TWO IN VITRO TESTS

1953 ◽  
Vol 9 (2) ◽  
pp. 224-231 ◽  
Author(s):  
W. R. PITNEY ◽  
T. RUSSELL FRASER
Keyword(s):  
Mode Of Action ◽  
Potassium Thiocyanate ◽  
The Other ◽  
Antithyroid Drugs ◽  
In Vitro Tests ◽  
Maximal Inhibition ◽  
Inhibitory Potency ◽  
Different Types ◽  
Oxidative Iodination

1. Two in vitro tests are described for measuring the inhibitory potency of antithyroid drugs on enzymic and non-enzymic oxidative iodination of protein; one, a milk enzymic iodination test, and the other an enzyme-free peroxide iodination test. 2. Five recognized antithyroid drugs have been tested: 2-thiouracil, 2-carbethoxythio-methyl-glyoxaline, potassium thiocyanate, resorcinol and sulphathiazole. By means of the milk enzymic test they could be ranged in order of potency, as indicated by the molar concentrations required for 50 % inhibition. They could also be separated into different types by the speed with which they pass from minimal to maximal inhibition with rising molar concentration. 3. With the enzyme-free peroxide test, thiouracil, but not resorcinol, was found to be inert; with the enzymic test, both were nearly equivalent in potency.

scholarly journals Participation of ATP in the binding of a yeast replicative complex to DNA.

1987 ◽  
Vol 246 (1) ◽  
pp. 213-219 ◽  
Author(s):  
S M Jazwinski
Keyword(s):  
Topoisomerase Ii ◽  
Relative Sensitivity ◽  
The Other ◽  
Functional Assay ◽  
Dna Topoisomerase Ii ◽  
Dna Complexes ◽  
Dna Topoisomerase ◽  
Initial Interaction ◽  
Atp Analogues

The activity that replicates yeast DNA in vitro can be isolated from cells of the budding yeast Saccharomyces in a high-Mr (approximately 2 × 10(6] form. Several lines of evidence indicate that this fraction contains a multiprotein replicative complex. A functional assay has been developed for the analysis of the interaction of the replicating activity with DNA. Binding of the activity required Mg2+, but did not require the addition of ATP or the other ribo- or deoxynucleoside triphosphates. However, the ATP analogues adenosine 5′-[gamma-thio]triphosphate and adenosine 5′-[beta gamma-imido]triphosphate blocked the binding, suggesting that ATP participates in the interaction at some stage. The binding was template (origin)-specific in either the presence or the absence of ATP and the other nucleoside triphosphates; however, ATP stabilized the replicating activity. The preferential inhibition of binding that was observed in the presence of the DNA topoisomerase II inhibitor coumermycin suggests that the requirement for ATP may be at least partially accounted for by the involvement of this enzyme in the initial interaction of the replicating activity with DNA. Finally, the binding was rapid. In contrast, DNA synthesis displayed a lag when assayed directly without first allowing a period for the replicating activity to bind to the DNA. In addition, binding was ‘tight’, as judged by the resistance of the protein–DNA complexes to salt in comparison with the relative sensitivity of binding. The replicating activity was not readily displaced from the complexes by exogenous DNAs, either possessing or lacking yeast origins of replication. The results suggest that the interaction of the replicating activity with the DNA occurs in more than one stage.

The Ellipticine Derivative NSC 338258 Has Anti-Myeloma Activity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3379-3379
Author(s):  
Erming Tian ◽  
Owen Stephens ◽  
Susan Holbeck ◽  
Bart Barlogie ◽  
John Shaughnessy
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Topoisomerase Ii ◽  
Kinase Inhibitor ◽  
Myeloma Cell ◽  
The Other ◽  
Response Analysis ◽  
Time Points ◽  
Cell Kill

Abstract We recently discovered that amplification and overexpression of the CKS1B gene, which regulates the ubiquitination and proteasomal degradation of the cyclin-dependent kinase inhibitor p27Kip1, is linked to a poor prognosis in myeloma. We used the COMPARE algorithm (NCI, Developmental Therapeutics Program) to identify correlations between the expression of CKS1B in the NCI 60 cell line panel and the GI50 of nearly 50,000 anticancer compounds. This analysis revealed a strong correlation between CKS1B expression and the anticancer activity of Ellipticine and multiple derivatives of it. Ellipticine (5,11-Dimethyl-6H-Pyrido[4,3]Carbazole, MW=246.3), an alkaloid isolated from Apocyanaceae, is a topoisomerase II poison that induces topoisomerase II-dependent DNA cleavages. Previous studies have shown that the anti-neoplastic mechanism of Ellipticine is to form covalent DNA adducts mediated by human cytochromes P450. We obtained Ellipticine and twelve other CKS1B-correlated antineoplastic compounds from the NCI-DTP. In vitro analyses were carried out with 12 myeloma cell lines. Cell viability was detected using CellTiter-Glo Luminescent Assay (Promega, Co.). We found that one of the Ellipticine derivatives, NSC 338258 (EPED3) showed significant cell kill activity not observed with Ellipticine or the other compounds in all cell lines tested. In a dose response analysis of cell kill using 0.2, 0.02, and 0.002 uM EPED3, 12 out of 12 myeloma cell lines showed at least 50% reduction in cell viability within 24 hrs at 0.2 uM compared to no treatment controls. By 48 hours essentially all cell growth was inhibited. Only weak to moderate cell kill was noted at 0.02 and 0.002 uM at all time points tested. We next tested the activity of the topoisomerase II inhibitor VP-16-213 at the same concentrations and time periods and found only modest reduction of cell viability at day 5 at 0.2uM. Essentially no effect on cell viability was observed at 0.02 and 0.002 uM at any of the time points tested. We next tested whether EPED3 had a comparable anti-myeloma activity as Adriamycin at the same concentrations. Twelve myeloma cell lines were exposed to EPED3, VP-16-213, and Adriamycin at 0.2mM for a total of 5 days. Results of the mean relative luminescence showed that EPED3 promoted an immediate cell proliferation arrest within the first 24 hours of culture, with almost complete cell kill within 3 days. The other drugs were less effective with Adriamycin inducing a > 90% reduction only after 4 days and VP-16 a > 70% reduction at day 5. These data suggests that EPED3 may represent a potential new therapeutic for myeloma. Studies are currently underway to test the efficacy of EPED3 in our in-vivo SCID-Hu mouse model of primary myeloma and results of these studies will be presented.

scholarly journals Searching for the mechanisms involved in Antimonium crudum action on macrophage – Leishmania interaction in vitro

2021 ◽  
Vol 17 (1) ◽  
pp. 02-04
Author(s):  
Leoni Villano Bonamin ◽  
Renata Rossetini Palombo ◽  
Carolina Shultz Morim ◽  
Sandra AG Pinto ◽  
Luciane Costa Dalboni ◽  
...  
Keyword(s):  
Biological Effect ◽  
Biological Effects ◽  
Pure Water ◽  
Image Analysis System ◽  
Gm Csf ◽  
Positive Effects ◽  
Physical Chemical ◽  
Wide Range

In previous studies [1,2] we showed that treatment of mice with Antimonium crudum (Ant-c) 30cH was able to significantly reduce monocyte migration to the infection site after injection of Leishmania (L) amazonensis into the subcutaneous tissue, resulting in clinical improvement. Follow up was performed with an in vitro model, which showed that treatment of co-cultures of RAW 264.7 macrophages and parasites with Ant-c 30cH inhibited two parasite-induced CCL2 peaks 48 and 120 hours after infection together with early inhibition of lysosome activity. These findings explained the results previously obtained in vivo. In turn, treatment with Ant-c 200cH resulted in an early and transitory peak of cell spreading at 48 hours. The coherence between the in vivo and in vitro results indicates that this is a good model to study more thoroughly the mechanisms of action of homeopathic medicines, being the first step to establish correlations between the biological effects and the physical and chemical features of Ant-c 30cH and 200cH. In the present study, the same experimental model was replicated, through comparison of vehicle (30% cereal alcohol), Ant-c 200cH, Zincum metallicum (Zinc) 200cH and Arsenicum album (Ars) 200cH, to confirm the specificity of Ant-c effects. In addition, Ant-c 200cH was ultra-centrifuged, and only the superficial phase was applied to the culture medium. This procedure intended to separate the heavier particles from the lighter ones suspended in the homeopathic medicine. The physical-chemical profile of the medicines was assessed. Solid contaminants (microparticles) in the suspension were analyzed. Conductivity was assessed through measurement of the electron current induced by a micro-amperimeter (Ryodoraku®) connected to 2 clean electrodes immersed in the samples, prepared immediately before the analysis, diluted in pure water (MilliQ, Millipore®) and filtered in 22-µ filter (Millipore®). Pure water was used as control. The device was calibrated immediately before measurements. The microparticle profile was assessed with a scanning electronic microscope - SEM (JEOL JSM 6510®) coupled to an energy dispersive spectroscopy (EDS) system to identify the nature of the elements present in each particle. The size and the number of particles were analyzed from the images generated by electronic microscopy with an automatic image analysis system (Metamorph®). For this purpose, all materials used was cleansed through immersion in pure acetone and subjected to 30-minute sonication before insertion into the microscope to avoid secondary contamination. The samples of medicines were subjected to ultra-centrifugation (10000rpm for 60 minutes) to induce particle sedimentation in the bottom of microtubes. 10 microliters of each sample were collected from the bottom of tubes and placed on a copper stub and kept in a closed recipient until the material was fully dry. The samples were directly analyzed with the microscope. Metallization was not necessary, because the analyzed particles had metallic nature. The biological effects of Ant-c 200cH reproduced the previous ones: spreading and phagocytosis index were significantly higher in the co-cultures treated with Ant-c 200cH compared to vehicle and other, non-specific treatments (Ars 200cH and Zinc 200cH) (p=0.05). However, these results were not exhibited by centrifuged Ant-c 200cH. Analysis of the supernatant after 48-hour incubation revealed increase of the GM-CSF content only in cultures treated with Ant-c 200cH and centrifuged-Ant-c 200cH. No change was observed in the cytokine profile in the cultures treated with Ars 200cH or Zinc 200cH. Morphological analysis of Ant-c samples on SEM showed that the microparticles in Ant-c 30cH were smaller compared to Ant-c 6cH, most of them having half-moon shape. Curiously, agglomerates of particles were detected in Ant-c 200cH. Contaminant particles suspended in pure water contained Pb, Zn, Ca, Na, Au, Hg, Nb and Si, therefore, not related to any specific biological effect of Ant-c. P was identified only in Ant-c 30cH (6.51%) and Ant-c 200cH (13.56%). This wide-range profile of different microparticles did not change after centrifugation, which indicates that the weight of these particles is not conditioned by the nature of their component elements. Conductivity was lower in the vehicle (30% alcohol) compared to Ant-c 6, 30 and 200cH (p=0.0001); the conductivity of Ant-c 200cH was the highest (p=0.008). Also Ars 200cH exhibited higher conductivity (p=0.001) compared to the vehicle. Taken together, these data suggest that the biological effect of Ant-c 200cH on macrophage spreading and phagocytosis might be partially related to the size of the microparticles found in suspension. However, specific effects relative to cytokine production did not depend on microparticle size or content. The changes in conductivity changes exhibited correlation with presence of some elements, such as P, but not with any biological effect. To summarize, the results point to the relevance of eventual false-positive effects relative to phagocytosis in macrophages treated with homeopathic medicines in vitro, due to the interference of larger sized microparticles. They also points to the specificity of GM-CSF expression after 48-hours of co-culture exposure to Ant-c 200cH, centrifuged or not, which suggests it was independent from microparticle content and conductivity. The physical-chemical features of homeopathic medicines related to their specific biological effects are still unknown. Additional studies are needed in this regard.

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