Continuous energy supply, a necessary condition for life, excites a state far from thermodynamic equilibrium, in particular coherent electric polar vibrations depending on water ordering in the cell. Disturbances in oxidative metabolism and coherence are a central issue in cancer development. Oxidative metabolism may be impaired by decreased pyruvate transfer to the mitochondrial matrix, either by parasitic consumption and/or mitochondrial dysfunction. This can in turn lead to disturbance in water molecules' ordering, diminished power, and coherence of the electromagnetic field. In tumors with the Warburg (reverse Warburg) effect, mitochondrial dysfunction affects cancer cells (fibroblasts associated with cancer cells), and the electromagnetic field generated by microtubules in cancer cells has low power (high power due to transport of energy-rich metabolites from fibroblasts), disturbed coherence, and a shifted frequency spectrum according to changed power. Therapeutic strategies restoring mitochondrial function may trigger apoptosis in treated cells; yet, before this step is performed, induction (inhibition) of pyruvate dehydrogenase kinases (phosphatases) may restore the cancer state. In tumor tissues with the reverse Warburg effect, Caveolin-1 levels should be restored and the transport of energy-rich metabolites interrupted to cancer cells. In both cancer phenotypes, achieving permanently reversed mitochondrial dysfunction with metabolic-modulating drugs may be an effective, specific anti-cancer strategy.
- Keywords
- LDH virus, cancer biophysics, disturbed coherence, microtubule oscillations, mitochondrial dysfunction, water ordering,
- Publication type
- Journal Article MeSH
- Review MeSH
Human and animal diseases are brought about by pathological alterations of production, composition, and conformation of macromolecules and structures in cells. Additional contributing factors include changes in physiological states caused by disturbances of energy supply, energy transduction, energy dissipation in moving or oscillating parts, and parasitic energy consumption. Disturbances of energy states may endanger existence of the system. The cell-mediated immunity (CMI) response of T lymphocytes correlating with their adherence properties was examined using antigen prepared from the serum of inbred laboratory mice strain C3H H(2k) infected with lactate dehydrogenase elevating (LDH) virus. LDH virus is a parasite on the cellular energy system. Significant CMI response was elicited in T lymphocytes prepared from the blood of patients with cancer of different phenotypes, acute myocardial infarctions, schizophrenia, and recurrent spontaneous abortions in early pregnancy from unknown reasons. The CMI response is assumed to monitor transferred information about decreased levels of energy states and decoherence in the cells caused by mitochondrial malfunction, parasitic consumption, production of lactate, and possibly other disturbances. The LDH virus infection or similar pathological processes caused by different agents might be connected with the diseases and monitored by the examined CMI response. A large amount of mitoses with chromosome defects in aborted fetuses suggest increased mutability of genomes caused by defective energy states.
- Keywords
- Cell-mediated immunity response, LDH virus antigen, acute myocardial infarction, cancer, pathological energy states, schizophrenia, spontaneous abortion from unknown reasons,
- MeSH
- Immunity, Cellular MeSH
- Energy Metabolism * MeSH
- Lactate dehydrogenase-elevating virus physiology MeSH
- Humans MeSH
- Mice MeSH
- Disease * MeSH
- T-Lymphocytes immunology MeSH
- Pregnancy MeSH
- Cell Survival MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
PURPOSE: To demonstrate the use of in vivo corneal confocal microscopy to reveal the reason for persistent disturbance of vision after a corneal abrasion. CASE REPORT: A 49-year-old man presented with a decrease in visual acuity and monocular diplopia after a traumatic corneal abrasion. Anterior segment optical coherence tomography was not beneficial. In vivo corneal confocal microscopy showed abnormal folding in the basal epithelial layer of the cornea. Based on these findings, a therapeutic abrasion of the affected epithelium was performed. Visual acuity returned to 1.0 after therapeutic abrasion, and overall findings on the eye were within physiological limits. Control corneal confocal microscopic examination confirmed reparation of the structure of epithelial cell layers. CONCLUSIONS: The in vivo corneal confocal microscopy can reveal corneal pathologic abnormality even in cases where other methods are not beneficial. Alongside other modern methods, it may become an important tool to help locate pathologic abnormality accurately and choose the proper therapeutic strategy.
- MeSH
- Debridement MeSH
- Wound Healing physiology MeSH
- Microscopy, Confocal * MeSH
- Middle Aged MeSH
- Humans MeSH
- Tomography, Optical Coherence MeSH
- Eye Injuries diagnosis etiology physiopathology surgery MeSH
- Vision Disorders diagnosis etiology physiopathology MeSH
- Epithelium, Corneal injuries pathology MeSH
- Wounds, Nonpenetrating diagnosis etiology physiopathology surgery MeSH
- Visual Acuity physiology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
Arterial hypertension is a serious health problem. Decompensation of blood pressure may cause many ocular complications. We present three case reports of men with decompensated blood pressure and associated ocular complications. Successful compensation of blood pressure leads to objective improvement of fundus changes and vision.
- MeSH
- Adult MeSH
- Hypertension complications physiopathology MeSH
- Blood Pressure * MeSH
- Middle Aged MeSH
- Humans MeSH
- Retinal Diseases diagnosis etiology MeSH
- Tomography, Optical Coherence MeSH
- Retina pathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
INTRODUCTION: Diabetic retinopathy is an important microvascular complication of diabetes as it threatens the vision. Diabetic maculopathy is the main cause of legal blindness in the adult population in western countries. The examination method involves digital fundus photography that enables comparison of the incidence, number as well as the size and the shape of pathological foci on the retina during patient visits. It, however, does not depict one important change--chronic retinal ischemia. This is identified using contrast imaging--fluorescein angiography (FAG). Administration of a contrast medium--fluorescein--into cubital vein enables depiction of non-perfused regions of the retina that form the basis for laser therapy indication as part of the prevention of proliferative diabetic retinopathy. Optical coherence tomography (OCT), during which an optical beam makes a cross-section through all 10 layers of the retina, is an important advance in the diagnostics of diabetic macular oedema. The spectral OCT (S-OCT) in particular is an analogy of a histological examination of retina but on a living tissue. RESULTS: Owing to the advances in examination techniques and treatment methods, diabetic neuropathy can now be diagnosed and treated. Early diagnosis of vascular and, consequently, tissue changes in the retina, and in its midsection in particular, is a prerequisite. Tight control of diabetes and the risk factors is sufficient to maintain good visual acuity in patients with intact inner blood-retinal barrier. In collaboration with a diabetologist, fenofibrates are used as the first line treatment when the inner blood-retinal barrier is disturbed (damaged tight junctions between endothelial cells of retinal vessels). To reduce focal macular oedema, the sources of fluid leakage into central retina are occluded using laser interventions on microaneurysms. In diffuse macular oedema, a more intensive laser technique using grid laser coagulation is applied to the central region as well as the surrounding areas of non-perfused retina. It is our view that major macular oedemas often result from an occlusion of a branch of retinal or macular venule. This is why we recommend complementing, in collaboration with a diabetologist, laser treatment of macular oedema with trombolytics. The aim of diabetic macular oedema treatment is its early elimination to avoid irreversible damage to the outer segments and later to photoreceptor cells. These changes are the main cause of the previously mentioned legal blindness in diabetic patients and are well identifiable on S-OCT. DISCUSSION: Laser therapy is the gold standard in the treatment of diabetic macular oedema as well as diabetic retinopathy. However, efficacy is lacking if diabetes and the risk factors are not tightly controlled. Instead of laser therapy to treat diabetic macular oedema with or without macular traction, some authors use a more expensive and more complicated surgery technique (pars plana vitrectomy with internal limiting membrane peeling) performed at early stages of the disease. CONCLUSION: Prevention of microangiopathy of retinal vessels through tight compensation of diabetes and the risk factors form the basis of successful treatment of diabetic retinopathy and maculopathy. At present, we are able to successfully treat developed diabetic retinopathy as well as maculaopathy, including stabilisation of visual function, subject to early diagnosis of retinal changes.
BACKGROUND: Central serous chorioretinopathy (CSC) is characterised by a serous detachment of the neurosensory retina in the macula. Chronic CSC tends to affect older individuals with a less favourable visual outcome. Photodynamic therapy (PDT) with verteporfin is a possible therapeutic approach in cases of CSC with no tendency for spontaneous resorption. PDT has shown good anatomic and functional results in treating chronic CSC. For the purpose of diminishing side effects, modifications of the standard protocol were used. MATERIALS AND METHODS: This is a retrospective study of 32 eyes with CSC of 32 patients treated by half-fluence PDT. The patients underwent complete ophthalmology examination. On optical coherence tomography (OCT) we measured central retinal thickness (CRT), the outer nuclear layer (ONL), presence of subfoveolar detachment of retinal pigment epithelium (PED), disturbance of external limiting membrane (ELM), morphological changes in the inner segment/outer segment (IS/OS) line and retinal pigment epithelium (RPE) atrophy. We evaluated at baseline, 3 and 12 months after PDT. RESULTS: The mean BCVA at baseline was 0.41 ± 0.23 log MAR, the mean BCVA at 3 months was 0.24 ± 0.20 and at the end of the follow-up it was 0.23 ± 0.200. We observed statistically significant improvements of visual acuity after 3 and 12 months (p < 0.001, Wilcoxon test). The mean central retinal thickness at baseline was 373 ± 87 µm, the mean CRT after 3 months was 234 ± 42 µm and after 12 months 223 ± 39 µm. A significant reduction from baseline was seen after 3 months and 12 months (p < 0.001, Wilcoxon test). Baseline ONL reached 80 ± 27 µm, after 3 months it was 78 ± 20 and after 12 months it was 74 ± 20 µm. We observed a statistically significant change in diminishing the amount of PED after PDT after 3 months and after 12 months (p = 0.021, McNemar's test). We observed that in patients with RPE ablation, there is lower chance for the restitution of the IS/OS layer (p = 0.045, Mann-Whitney test). We observed a negative association between the improvement of visual acuity after 12 months and the presence of RPE ablation (p = 0.031, Mann-Whitney test). Restitution of ELM was significantly more often in patients with shorter duration of symptoms, (p = 0.027 after 3 months, p = 0.033 after 12 months after PDT, Spearman correlation). Neither ocular nor systemic adverse effects were observed during the follow-up period. CONCLUSIONS: Half-fluence PDT treatment has shown to be a usually safe and often effective therapy in patients with chronic CSC. This study suggests that the most important predictive factor is baseline visual acuity. The important anatomical change detected using OCT is a thinning of the outer nuclear layer. Nonetheless, other studies with a larger number of patients and a longer follow-up are required.
- Keywords
- Central serous chorioretinopathy, chronic, morphological changes, optical coherence tomography, photodynamic therapy,
- MeSH
- Central Serous Chorioretinopathy diagnosis drug therapy physiopathology MeSH
- Chronic Disease MeSH
- Adult MeSH
- Fluorescein Angiography MeSH
- Photochemotherapy methods MeSH
- Photosensitizing Agents therapeutic use MeSH
- Fundus Oculi MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Tomography, Optical Coherence MeSH
- Porphyrins therapeutic use MeSH
- Retinal Pigment Epithelium pathology MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Verteporfin MeSH
- Treatment Outcome MeSH
- Visual Acuity * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Photosensitizing Agents MeSH
- Porphyrins MeSH
- Verteporfin MeSH
The study provides an up-to-date overview of pathogenesis, functional and structural changes in normal tension glaucoma (NTG) and its differences from high tension glaucomas (HTG). The authors point to less known facts which make both diagnostic groups different. First of all, there are electrophysiological findings that verify pathology in the complete visual pathway in HTG in contrast to NTG where the retinal ganglion cell response is relatively normal but the abnormalities are in the visual pathway. This corresponds to the findings of functional magnetic resonance imaging of the brain with a significant decrease in activity in HTG compared to NTG. We found a higher decrease in activity in HTG following application of the colour paradigm compared to NTG where we did not see a similar difference. We also investigated the central corneal thickness (CCT) in both diagnostic groups. We did not find a statistically significant difference. However, we found the effect of CCT on progression of the changes in visual fields in HTG. In relation to suspicion of abnormally low cerebrospinal pressure and a possible cerebrovascular fluid flow disturbance in NTG, we examined the optic nerve thickness (OND) and optic nerve sheath diameter (OSD) at a distance of 4, 8, 16 and 20mm from the posterior pole of the eye. In the comparison with the healthy population, we did not find any abnormalities except for the width of the optic chiasma that was markedly lower in NTG. In relation to a possible impairment of cerebral perfusion we determined the degrees of cerebral atrophy using magnetic resonance imaging by measuring the bicaudate ratio (BCR) and white matter lesions using the Fazekas scale. We did not find a difference between HTG and NTG in BCR. We found statistically significant changes in BCR which correlated with the changes in visual fields. The higher values of the pattern defect were associated with increased brain atrophy (BCR). We did not detect similar relations in the Fazekas scale. We found a significant difference in this parameter among NTG, HTG and a control group. We found the most advanced changes in the patients with HTG. Conclusion: In HTG, impairment of retinal ganglion cells and subsequently also their axons, including visual cortex occurs because of a high intraocular pressure. In NTG, the retinal ganglion cells are relatively normal like the visual cortex, but alteration occurs in their axons. The cause is not a high intraocular pressure but most probably ischemia.
- Keywords
- differences from high tension glaucomas, normal tension glaucoma, structural and functional changes,
- MeSH
- Optic Disk * MeSH
- Glaucoma, Open-Angle * diagnosis therapy MeSH
- Glaucoma * MeSH
- Humans MeSH
- Intraocular Pressure MeSH
- Tomography, Optical Coherence MeSH
- Visual Field Tests MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Over the last decades, the natural disturbance is increasingly putting pressure on European forests. Shifts in disturbance regimes may compromise forest functioning and the continuous provisioning of ecosystem services to society, including their climate change mitigation potential. Although forests are central to many European policies, we lack the long-term empirical data needed for thoroughly understanding disturbance dynamics, modeling them, and developing adaptive management strategies. Here, we present a unique database of >170,000 records of ground-based natural disturbance observations in European forests from 1950 to 2019. Reported data confirm a significant increase in forest disturbance in 34 European countries, causing on an average of 43.8 million m3 of disturbed timber volume per year over the 70-year study period. This value is likely a conservative estimate due to under-reporting, especially of small-scale disturbances. We used machine learning techniques for assessing the magnitude of unreported disturbances, which are estimated to be between 8.6 and 18.3 million m3 /year. In the last 20 years, disturbances on average accounted for 16% of the mean annual harvest in Europe. Wind was the most important disturbance agent over the study period (46% of total damage), followed by fire (24%) and bark beetles (17%). Bark beetle disturbance doubled its share of the total damage in the last 20 years. Forest disturbances can profoundly impact ecosystem services (e.g., climate change mitigation), affect regional forest resource provisioning and consequently disrupt long-term management planning objectives and timber markets. We conclude that adaptation to changing disturbance regimes must be placed at the core of the European forest management and policy debate. Furthermore, a coherent and homogeneous monitoring system of natural disturbances is urgently needed in Europe, to better observe and respond to the ongoing changes in forest disturbance regimes.
- Keywords
- European forests, bark beetles, climate change, empirical disturbance data, fire, forest natural disturbances, windstorms,
- MeSH
- Coleoptera * MeSH
- Ecosystem * MeSH
- Forests MeSH
- Trees MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
Mitochondrial dysfunction is a central defect in cells creating the Warburg and reverse Warburg effect cancers. However, the link between mitochondrial dysfunction and cancer has not yet been clearly explained. Decrease of mitochondrial oxidative energy production to about 50 % in comparison with healthy cells may be caused by inhibition of pyruvate transfer into mitochondrial matrix and/or disturbed H+ ion transfer across inner mitochondrial membrane into cytosol. Lowering of the inner membrane potential and shifting of the working point of mitochondria to high values of pH above an intermediate point causes reorganization of the ordered water layer at the mitochondrial membrane. The reorganized ordered water layers at high pH values release electrons which are transferred to the cytosol rim of the layer. The electrons damp electromagnetic activity of Warburg effect cancer cells or fibroblasts associated with reverse Warburg effect cancer cells leading to lowered electromagnetic activity, disturbed coherence, increased frequency of oscillations and decreased level of biological functions. In reverse Warburg effect cancers, associated fibroblasts supply energy-rich metabolites to the cancer cell resulting in increased power of electromagnetic field, fluctuations due to shift of oscillations to an unstable nonlinear region, decreased frequency and loss of coherence.
- Keywords
- Warburg effect, biological electromagnetic activity, cancer, mitochondrial dysfunction, mitochondrial membrane potential, water ordering,
- MeSH
- Electromagnetic Fields * MeSH
- Fibroblasts pathology MeSH
- Hydrogen-Ion Concentration MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Mitochondria pathology MeSH
- Neoplasms pathology MeSH
- Oscillometry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Coherent vibration states in biological systems excited in nonlinear electrically polar structures by metabolic energy supply were postulated by H. Fröhlich. Fröhlich's requirements for coherent vibrations and generation of electromagnetic field are satisfied by microtubules whose subunits are electric dipoles. Static electric field around mitochondria and "wasted energy" efflux from them provide nonlinear conditions and coherent excitation. Numerical models are used for analysis of coherent vibration states. A hypothesis is presented that dysfunction of mitochondria (i.e., extinction of the zones of the static electric field and of the efflux of "wasted energy") and disintegration of the cytoskeleton on the pathway of cancer transformation result in disturbances of coherence of the cellular electrically polar oscillations and of the generated electromagnetic field with consequences in cellular organization and interactions between cells. Local invasion, detachment, and metastasis of cancer cells are subsequent events of disturbed electromagnetic interactions.
- MeSH
- Biophysical Phenomena * MeSH
- Models, Biological MeSH
- Cytoskeleton metabolism radiation effects MeSH
- Electromagnetic Fields adverse effects MeSH
- Humans MeSH
- Mitochondria metabolism radiation effects MeSH
- Cell Transformation, Neoplastic radiation effects MeSH
- Cell Line, Tumor MeSH
- Neoplasms pathology MeSH
- Nonlinear Dynamics MeSH
- Vibration MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
