Can Administration of Potentized Homeopathic Remedy, Arsenicum Album, Alter Antinuclear Antibody (ANA) Titer in People Living in High-Risk Arsenic Contaminated Areas? I. A Correlation with Certain Hematological Parameters

To examine whether elevated antinuclear antibody (ANA) titers reported in random human population of arsenic contaminated villages can be reverted to the normal range by administration of a potentized homeopathic drug, Arsenicum album, randomly selected volunteers in two arsenic contaminated villages and one arsenic-free village in West Bengal (India) were periodically tested for their ANA titer as well as various blood parameters in two types of experiments: ‘placebo-controlled double blind’ experiment for shorter duration and ‘uncontrolled verum fed experiment’ for longer duration. Positive modulation of ANA titer was observed along with changes in certain relevant hematological parameters, namely total count of red blood cells and white blood cells, packed cell volume, hemoglobin content, erythrocyte sedimentation rate and blood sugar level, mostly within 2 months of drug administration. Thus, Arsenicum album appears to have great potential for ameliorating arsenic induced elevated ANA titer and other hematological toxicities

Can Homeopathic Arsenic Remedy Combat Arsenic Poisoning in Humans Exposed to Groundwater Arsenic Contamination?: A Preliminary Report on First Human Trial

Groundwater arsenic (As) has affected millions of people globally distributed over 20 countries. In parts of West Bengal (India) and Bangladesh alone, over 100 million people are at risk, but supply of As-free water is grossly inadequate. Attempts to remove As by using orthodox medicines have mostly been unsuccessful. A potentized homeopathic remedy, Arsenicum Album-30, was administered to a group of As affected people and thereafter the As contents in their urine and blood were periodically determined. The activities of various toxicity marker enzymes and compounds in the blood, namely aspartate amino transferase, alanine amino transferase, acid phosphatase, alkaline phosphatase, lipid peroxidation and reduced glutathione, were also periodically monitored up to 3 months. The results are highly encouraging and suggest that the drug can alleviate As poisoning in humans

Dopamine Regulates Angiogenesis in Normal Dermal Wound Tissues

Cutaneous wound healing is a normal physiological process and comprises different phases. Among these phases, angiogenesis or new blood vessel formation in wound tissue plays an important role. Skin is richly supplied by sympathetic nerves and evidences indicate the significant role of the sympathetic nervous system in cutaneous wound healing. Dopamine (DA) is an important catecholamine neurotransmitter released by the sympathetic nerve endings and recent studies have demonstrated the potent anti-angiogenic action of DA, which is mediated through its D2 DA receptors. We therefore postulate that this endogenous catecholamine neurotransmitter may have a role in the neovascularization of dermal wound tissues and subsequently in the process of wound healing. In the present study, the therapeutic efficacy of D2 DA receptor antagonist has been investigated for faster wound healing in a murine model of full thickness dermal wound. Our results indicate that treatment with specific D2 DA receptor antagonist significantly expedites the process of full thickness normal dermal wound healing in mice by inducing angiogenesis in wound tissues. The underlined mechanisms have been attributed to the up-regulation of homeobox transcription factor HoxD3 and its target α5β1 integrin, which play a pivotal role in wound angiogenesis. Since D2 DA receptor antagonists are already in clinical use for other disorders, these results have significant translational value from the bench to the bedside for efficient wound management along with other conventional treatment modalities

Effect of eticlopride treatment on macroscopic aspect of wound closure and formation of new blood vessels in wound bed.

<p>(<b>A</b>) The treatment with eticlopride, a specific D₂ dopamine receptor antagonist; 10 mg/kg/4 days/i.p. significantly accelerated the rate of wound healing with resurfacing occurring by 9 days whereas complete wound closure in controls occurred on day 14. The control group received similar volume of normal saline only. (<b>B</b>) Wound closure analysis. In treatment group of mice eticlopride significantly accelerated wound closure compared to vehicle treated control (each group, n = 6; *, P<0.05). Time to wound closure was defined as the time until the re-epithelialization process was complete and the wound bed was filled with new tissues. The percentage of wound closure was calculated as: (area of original wound − area of actual wound) x100/area of original wound and were measured by analyzing images using an image analysis program (ImageJ, NIH). (<b>C</b>) Immunohistochemical staining of CD31, a specific endothelial cell surface marker to enumerate the number of microvessels. The figure shows significantly greater number of microvessels (reddish brown in color) in wound tissue sections of eticlopride treated mice in comparison to vehicle treated controls. Original magnifications, × 100. (<b>D</b>) Graphical representation shows significantly higher number of microvessels in eticlopride treated groups when compared to vehicle treated controls at day 5, 24 hours after completion of treatment schedule. Microvessel density was measured by counting the number of microvessels in 10 randomly chosen high power microscopic fields within the sections,*, P<0.05). Results are representative of six separate experiments each yielding similar results.</p

Effect of eticlopride treatment on expression of HoxD3 and its target α5β1 integrin in cutaneous wound tissue of mice.

<p>(<b>A</b>) Immunoprecipitation followed by immunoblot analysis of HoxD3 expression in wound tissues of both eticlopride and saline treated wound bearing mice at day 5 post wounding. The immunoblot analysis shows significantly higher expression of HoxD3 protein in wound tissues of eticlopride treated mice than vehicle treated controls at 5^th day after creation of wounds. (<b>B</b>) The bar graphs represent the density of each HoxD3 protein band relative to the IgG expression as quantified by ImageJ (NIH), *, P<0.05. (<b>C</b>) Immunohistochemical analysis of the expression of α5β1 integrin in cutaneous wound tissues of both control and eticlopride treated mice at day 5 post wounding. Frozen sections were immunostained with anti-α5β1 integrin antibodies followed by biotin conjugated secondary antibodies. The sections were stained using ABC staining kit and Nova-Red substrate solution to develop color. Significantly more areas of wound bed show positive staining (reddish brown color) for α5β1 integrin following eticlopride treatment. Original magnifications, x 100. Results are representative of six separate experiments each yielding similar results.</p

D₂ Dopamine receptors are present on the surface of human umbilical vein endothelial cells.

<p>(<b>A</b>) Immunoblot shows presence of D₂ dopamine receptors in HUVEC. (<b>B</b>) Flow cytometric analysis of D₂ dopamine Receptors in HUVEC. Over 81% cells of the total HUVEC population express D₂ dopamine receptors on their surfaces as evident from the lower right quadrant.</p

Dopamine through its D₂ receptors can significantly downregulate VEGF induced expressions of HoxD3 and its target genes α5 and β1 integrins in HUVEC.

<p>(<b>A, B and C</b>) Western blot analysis of the effect of dopamine on VEGF induced expressions of HoxD3 and its target genes α5 and β1 integrins in HUVEC. Lane 1: Serum starved Human Umbilical Vein Endothelial Cells show no expression of HoxD3. However expression of both α5 and β1 integrins was observed. Lane 2: Cells stimulated with VEGF (10 ng/ml) show significant expression of HoxD3 and both the integrins after 8 hours of stimulation. Lane 3: Cells pretreated with 1 µM dopamine (concentration of DA found in synaptic clefts) 5 minutes before being exposed to VEGF (10 ng/ml) show significantly down-regulated VEGF induced expression of HoxD3 and both α5 and β1 integrins compared with VEGF treated controls. Lane 4: Cells treated with 100 µM eticlopride followed by dopamine and VEGF. Pre-treatment with eticlopride abrogated dopamine-induced down-regulation of HoxD3 and its target α5 and β1 integrin expression in HUVEC. β-actin was used as loading controls. Results are representative of six separate experiments each yielding similar results. (<b>D, E and F</b>) The bar graphs represent the density of each protein band relative to the β-actin expression. These have been quantified by ImageJ (NIH), *, P<0.05.</p

(–) Typical skin symptom on palms (upper row) and soles (lower row) of a victim before (left) and 2 months (right) after administration of Arsenicum Album-30

<p><b>Copyright information:</b></p><p>Taken from "Can Homeopathic Arsenic Remedy Combat Arsenic Poisoning in Humans Exposed to Groundwater Arsenic Contamination?: A Preliminary Report on First Human Trial"</p><p>Evidence-based Complementary and Alternative Medicine 2005;2(4):537-548.</p><p>Published online 19 Oct 2005</p><p>PMCID:PMC1297497.</p><p>© The Author (2005). Published by Oxford University Press. All rights reserved.</p