Comparative efficacy of two microdoses of a potentized homoeopathic drug, Cadmium Sulphoricum, in reducing genotoxic effects produced by cadmium chloride in mice: a time course study

BACKGROUND: Cadmium poisoning in the environment has assumed an alarming problem in recent years. Effective antimutagenic agents which can reverse or combat cadmium induced genotoxicity in mice have not yet been reported. Therefore, in the present study, following the homeopathic principle of "like cures like", we tested the efficacy of two potencies of a homeopathic drug, Cadmium Sulphoricum (Cad Sulph), in reducing the genotoxic effects of Cadmium chloride in mice. Another objective was to determine the relative efficacy of three administrative modes, i.e. pre-, post- and combined pre and post-feeding of the homeopathic drugs. For this, healthy mice, Mus musculus, were intraperitoneally injected with 0.008% solution of CdCl(2) @ 1 ml/100 gm of body wt (i.e. 0.8 mcg/gm of bw), and assessed for the genotoxic effects through such studies as chromosome aberrations (CA), micronucleated erythrocytes (MNE), mitotic index (MI) and sperm head anomaly (SHA), keeping suitable succussed alcohol fed (positive) and CdCl(2) untreated normal (negative) controls. The CdCl(2) treated mice were divided into 3 subgroups, which were orally administered with the drug prior to, after and both prior to and after injection of CdCl(2) at specific fixation intervals and their genotoxic effects were analyzed. RESULTS: While the CA, MNE and SHA were reduced in the drug fed series as compared to their respective controls, the MI showed an apparent increase. The combined pre- and post-feeding of Cad Sulph showed maximum reduction of the genotoxic effects. CONCLUSIONS: Both Cad Sulph-30 and 200 were able to combat cadmium induced genotoxic effects in mice and that combined pre- and post-feeding mode of administration was found to be most effective in reducing the genotoxic effect of CdCl(2) followed by the post-feeding mode

Gene-expression profiling of different arms of lymphatic vasculature identifies candidates for manipulation of cell traffic

Afferent lymphatic vessels bring antigens and diverse populations of leukocytes to draining lymph nodes, whereas efferent lymphatics allow only lymphocytes and antigens to leave the nodes. Despite the fundamental importance of afferent vs. efferent lymphatics in immune response and cancer spread, the molecular characteristics of these different arms of the lymphatic vasculature are largely unknown. The objective of this work was to explore molecular differences behind the distinct functions of afferent and efferent lymphatic vessels, and find possible molecules mediating lymphocyte traffic. We used laser-capture microdissection and cell sorting to isolate lymphatic endothelial cells (LECs) from the subcapsular sinus (SS, afferent) and lymphatic sinus (LS, efferent) for transcriptional analyses. The results reveal marked differences between afferent and efferent LECs and identify molecules on lymphatic vessels. Further characterizations of Siglec-1 (CD169) and macrophage scavenger receptor 1 (MSR1/CD204), show that they are discriminatively expressed on lymphatic endothelium of the SS but not on lymphatic vasculature of the LS. In contrast, endomucin (EMCN) is present on the LS endothelium and not on lymphatic endothelium of the SS. Moreover, both murine and human MSR1 on lymphatic endothelium of the SS bind lymphocytes and in in vivo studies MSR1 regulates entrance of lymphocytes from the SS to the lymph node parenchyma. In conclusion, this paper reports surprisingly distinct molecular profiles for afferent and efferent lymphatics and a function for MSR1. These results may open avenues to explore some of the now-identified molecules as targets to manipulate the function of lymphatic vessels

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

BACKGROUND: This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. DISCUSSION: The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. SUMMARY: Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine

Features of surgical access during videothoracoscopy operations in the wounded with chest trauma

To improve the treatment of wounded with combat chest injury by optimizing low-traumatic surgical access using video thoracoscopy. Materials and methods. In the period from 2014 to 2019, 103 injured were treated with video-assisted thoracoscopic surgical interventions in case of chest trauma. According to the objectives of the study, two clinical groups of victims were formed. The comparison group included 54 (52.4 %) victims, the main group – 49 (47.6 %). The wounded accounted for 72 persons (69.9 %), injured – 31 (30.1 %). In case of wounds to the chest, the selection of victims for VTS surgical interventions and the timing of their implementation was carried out taking into account the location, type of injury and trauma, the severity of the condition of the patients, the presence of a combined wound, the possibility of two or one-lung ventilation during the intervention, the timing of admission to a medical institution with the moment of injury, the technical capabilities of military-technical operations. In staging trocars during combat chest injury, we adhere to the general rules for video-assisted thoracoscopic interventions on the chest – the rules of the “triangle”. When a chest injury is involved, the port setting has its variability, which is based on the type of injury and the purpose of the surgical intervention. You can use both standard points of installation of thoracoports, and non-standard individual ones that will correspond to the set clinical goals. Research results and discussion. High efficiency in visualization of the operating area and the technical convenience of surgical techniques have been established. This allows a rational and consistent audit of the anatomical zone of the wound. With a chest injury, the most rational sequence for conducting a pleural cavity audit is on the principle of paramount importance. Conclusions. Features of online access – port setting for injuries to the chest depends on the area of the inlet of the gunshot. When setting ports, it is not necessary to adhere to standard points, the introduction of a thoracoport is possible at any point on the chest wall, but with the obligatory observance of the triangulation rule. The number of input ports for combat trauma to the chest depends on the technical need for a full operation. In the vast majority of military-technical operations, 3 thoracoports are enough

Karyomorphological studies in three species of Teleostean fishes

The diploid number, karyomorphology and morphometrical analysis of metaphase chromosomes in three teleostean fishes have been studied from the kidney cells of the female after colchicine-citrate-flame drying-Giemsa technique. Mystus gulio (Fam: Bagridae) possesses 2n=58 with chromosome formula as n=15 m+6sm+1st+7 T (NF 102) and the mean length values ranging between 1.90 and 0.77 micron from the longest to the shortest chromosome. Eutropiichthys vacha (Fam: Schilbeidae) have also 2n=58 chromosomes, but with the formula of n=5 m+10sm+6st+2t+6 T (NF 100) and the mean length values of chromosomes from 1.73 to 0.67 micron. Mastacembelus armatus (Fam: Mastacembelidae) have 2n=48 chromosomes with the formula as n=5 m+2sm+1st+16 T (NF 64) and the mean length values ranged between 1.81 and 0.89 micron. The karyotypes of these species have been compared with the related ones and it has been suggested that pericentric inversion played the significant role in the evolution of their karyotypes