Tissue distribution and biochemical properties of an interspecific tumour-associated gamma foetal antigen.

A late-gestation neonatal antigen (gamma foetal antigen; gamma-FA) immunologically and biochemically unrelated to murine alpha-foetoprotein, was identified in several spontaneous and carcinogen-induced sarcomas and hepatic carcinomas of the mouse and rat. An approximate mol. wt of 35,000 for gamma-FA from both foetus and tumour was obtained by molecular-sieve chromatography and sucrose-gradient centrifugation. Radial immunodiffusion analyses of organ extracts indicated that gamma-FA could be found in several neonatal tissues, the highest concentration occurring in the spleen. In the 2-month-old mouse, only splenic tissue contained gamma-FA and at much lower levels than in the organ of the newborn mouse

Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers

<p>Abstract</p> <p>Background</p> <p>In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system.</p> <p>Methods</p> <p>We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both <it>in vitro </it>in immune cells from mice and human, and <it>in vivo </it>in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after <it>in vitro </it>treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice <it>in vivo </it>treatment.</p> <p>Results</p> <p>None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS)-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α) release and M1, and M8 decreased IFN-<it>γ </it>production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. <it>In vivo </it>treatment lead to a decrease in reactive oxygen species (ROS), nitric oxide (NO) production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity.</p> <p>Conclusions</p> <p>Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised.</p

Anti-Helicobacter pylori activity and immunostimulatory effect of extracts from Byrsonima crassa Nied. (Malpighiaceae)

<p>Abstract</p> <p>Background</p> <p>Several <it>in vitro </it>studies have looked at the effect of medicinal plant extracts against <it>Helicobacter pylori </it>(<it>H. pylori</it>). Regardless of the popular use of <it>Byrsonima crassa </it>(<it>B. crassa</it>) as antiemetic, diuretic, febrifuge, to treat diarrhea, gastritis and ulcers, there is no data on its effects against <it>H. pylori</it>. In this study, we evaluated the anti-<it>H. pylori </it>of <it>B. crassa </it>leaves extracts and its effects on reactive oxygen/nitrogen intermediates induction by murine peritoneal macrophages.</p> <p>Methods</p> <p>The minimal inhibitory concentration (MIC) was determined by broth microdilution method and the production of hydrogen peroxide (H₂O₂) and nitric oxide (NO) by the horseradish peroxidase-dependent oxidation of phenol red and Griess reaction, respectively.</p> <p>Results</p> <p>The methanolic (MeOH) and chloroformic (CHCl₃) extracts inhibit, <it>in vitro</it>, the growth of <it>H. pylori </it>with MIC value of 1024 μg/ml. The MeOH extract induced the production H₂O₂and NO, but CHCl₃extract only NO.</p> <p>Conclusion</p> <p>Based in our results, <it>B. crassa </it>can be considered a source of compounds with anti-<it>H. pylori </it>activity, but its use should be done with caution in treatment of the gastritis and peptic ulcers, since the reactive oxygen/nitrogen intermediates are involved in the pathogenesis of gastric mucosal injury induced by ulcerogenic agents and <it>H. pylori </it>infections.</p

The in vitro toxicology of Swedish snus

Three commercial brands of Swedish snus (SWS), an experimental SWS, and the 2S3 reference moist snuff were each tested in four in vitro toxicology assays. These assays were: Salmonella reverse mutation, mouse lymphoma, in vitro micronucleus, and cytotoxicity. Water extractions of each of the 5 products were tested using several different concentrations; the experimental SWS was also extracted using dimethyl sulfoxide (DMSO). Extraction procedures were verified by nicotine determinations. Results for SWS in the mutagenicity assays were broadly negative: there were occasional positive responses, but these were effectively at the highest concentration only (concentrations well above those suggested by regulatory guidelines), and were often associated with cytotoxicity. The 2S3 reference was unequivocally positive in one of the three conditions of the micronucleus assay (MNA), at the highest concentration only. Positive controls produced the expected responses in each assay. The SWS data are contrasted with data reported for combusted tobacco in the form of cigarettes, where strongly positive responses have been routinely reported for mutagenicity and cytotoxicity. These negative findings in a laboratory setting concur with the large amount of epidemiological data from Sweden, data showing that SWS are associated with considerably lower carcinogenic potential when compared with cigarettes

In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug

The anti-tumour effects and mechanism of action of combretastatin A-4 and its prodrug, combretastatin A-4 disodium phosphate, were examined in subcutaneous and orthotopically transplanted experimental colon tumour models. Additionally, the ability of these compounds to directly interfere with endothelial cell behaviour was also examined in HUVEC cultures. Combretastatin A-4 (150 mg kg–1, intraperitoneally (i.p.)) and its water-soluble prodrug (100 mg kg–1, i.p.) caused almost complete vascular shutdown (at 4 h), extensive haemorrhagic necrosis which started at 1 h after treatment and significant tumour growth delay in MAC 15A subcutaneous (s.c.) colon tumours. Similar vascular effects were obtained in MAC 15 orthotopic tumours and SW620 human colon tumour xenografts treated with the prodrug. More importantly, in the orthotopic models, necrosis was seen in vascularized metastatic deposits but not in avascular secondary deposits. The possible mechanism giving rise to these effects was examined in HUVEC cells. Here cellular networks formed in type I calf-skin collagen layers and these networks were completely disrupted when incubated with a non-cytotoxic concentration of combretastatin A-4 or its prodrug. This effect started at 4 h and was complete by 24 h. The same non-cytotoxic concentrations resulted in disorganization of F-actin and β-tubulin at 1 h after treatment. In conclusion, combretastatin A-4 and its prodrug caused extensive necrosis in MAC 15A s.c. and orthotopic colon cancer and metastases, resulting in anti-tumour effects. Necrosis was not seen in avascular tumour nodules, suggesting a vascular mechanism of action. © 1999 Cancer Research Campaig