BiTherapca Health

Chronic infections start as acute infections. Some acute infections resolve while others take a chronic course. The infective agent as well as the immune system plays an active role in  the outcome of the disease. Normally, most infections are resolved, aided by treatment or not, by phagocytosis when the microbes are still in their discrete, planktonic forms. To start with, mast cells degranulate, in the presence of an infective agent, or a solid particle that provides shear strain or stress-- and may eventually lead to allergy if antigenic. Allergens cause the cross-linking of IgE on mast cells and the mechanical shear therefrom causes degranulation. Mast cell degranulation releases histamine, heparin, prostaglandin D2, leukotriene C4 as well as chymase and tryptase--serine proteases, hydrogen peroxide, oxygen free radicals and NO. This leads to increased capillary permeability, and fleeting hives may form. Leucocyte migration leads...

Just as intrinsic immunity takes care of an internalized(intra-cellular) infection, each normal cell(non-professional phagocyte) is capable of  'eating' an apoptotic cell that results from environmental damage like UV radiation and mechanical shear strain and stress. Repair, including the rapid reconstitution of the cell membrane, will prevent apoptosis, following such damage. However, for the most part, it is the availability of neighboring healthy cells, which recognize the 'eat me' signal on these damaged cells, that is responsible for clearing the mess in time before the damaged cells, themselves, become toxic, as they spill out their content. More severe damage, however, will permit some of the content to fleet about and this will allow the immune cells to sense, approach and mop up the mess, at the same time suffering injuries of their own, and causing more inflammation, by virtue of their stem-cell-like fragility and inherent ability...

Every cell has an inherent ability to fight an indwelling infection. Intrinsic immunity helps fight intracellular infections that seek to maintain latency. It does so by increasing gene expression and so enabling the replication of the virus. Janus kinase(JAK), a tyrosine kinase, activated by the stress hormone, cortisol, increases gene expression by temporarily phosphorylating transcription factors and methylated bases of the DNA; activating gene expression and increasing metabolism. Cytokines for the JAK-STAT pathway activate viruses which replicate, and this leads to cell death. Active viral replication prompts this intrinsic immune response through inducing apoptosis, which is highly regulated. Arginine demethylase implicated in increased gene expression, and providing oxidative stress marker on protein Brf2, a survival protein, will inevitably lead to apoptosis. An apoptotic cell then exposes phosphatidylserine, an 'eat me' signal, that prompts phagocytosis and the elimi...

Cellular proliferation with growth is an energy-intensive and substrate-demanding process. Food availability and growth factors work together to make this happen. Metabolism is at the center of this. Glycolysis and glutaminolysis are enhanced and storage as lactic acid and malic acid helps draw on lipolysis to supply the Krebs cycle for the tissue building intermediates and NADH, FADH2 and GTP; and much more ATP therefrom, in oxidative phosphorylation. In cellular proliferative and growth states, glycolic metabolism provides steady supply of acetyl CoA, which now does not get to the mitochondria, already preoccupied with the formed acetyl CoA, from the mitochondrial beta oxidation of lipids, to form citrate and sustain the citrate cycle. The cycle then provides the metabolic building blocks and ATP for anabolism, as glycolysis is providing acetyl CoA, for lipogenesis and cholesterolgenesis, used in building the cell membrane and for the synthesis of growth steroids, as well as for hi...

Stress leads to cellular damage which necessitates frank cellular repair and growth; apoptosis, or necrosis and inflammation, that will prompt cellular proliferation and growth. For the first mechanism to happen, there must be ant-stress strategic mechanisms in place, and operational, that prevent overt damage or are rapidly mobilized to take care of the damage before cell death ensues or inflammation and cellular proliferation take place to remedy tissue deficiency. These include repair enzymes, anti-oxidants and the rapid mobilization of food resources. A well nourished body will take this path and full tissue restoration is more likely. On the other hand, apoptosis, or necrosis including necroptosis, will result if there is not enough protective mechanisms, the damage is excessive, repair is defective or nutritional resources are inadequate. Some tissue reorganization is more likely and recovery is unlikely to be full. Growth hormone and proliferative factors and co-factors...

Metabolism involves catabolism and anabolism. These two usually go in tandem such that as there is more breakdown of food, there is a complementary buildup of tissue. Tissue breakdown in autophagy supplies the nutrients and energy, necessary for tissue recycling and rejuvenation, through the intermediary of growth factors and the growth hormone. However, dietary food supply provides excessive amount of carbohydrates and fats that breakdown to form de novo fat, which through insulin, is stored and in addition to tissue buildup from available amino acids from dietary protein. High AMP prevents metabolism due to inability of enzymes, principally tyrosine kinases, to phosphorylate target proteins and DNA and ramp up metabolism. AMP synthetase, in response, goes into action to promote autophagy, the breakdown of tissue proteins, and stored carbohydrates and lipids, and ramp up metabolism. This is a compensatory mechanism that coincides with the activation of adenylate cyclase which now p...

An irrefutable body of research continues to cumulate, showing that physical exercise is good for health. Its obvious and desirable effects are on lean body weight and muscle tone which are good for esthetics, wellness and fitness. Especially astounding are the health benefits it gives. Exercise promotes autophagy, which in normal 'doses', is followed by rejuvenation of tissue through growth factors and, from prompting protective antioxidant mechanisms, sensed by increased NAD/DADH ratio, which governs the epigenetics of histone deacetylation. A higher or prolonged 'dose' of exercise will lead to more drastic autophagy and increased pRb-dependent mitochondrial metabolism that produces oxygen free radicals which in turn favor cell death--and so it is anticancer, and pRb is an anti-oncogene, being a tumor suppressor, in this capacity. It, however, turns out that pRb may become oncogenic when in the presence of a proto-oncogene such as growth factors, since apoptosi...

It is becoming more and more clear that the living cell via its genome is aware of and senses its environment and adjusts(adapts) to it. The environment, on its own part, affects the genes directly through mutations or indirectly, by modifying their expression, epigenetically in a physical or steric alteration of the heterochromatin and euchromatin, and with the introduction of chemical tags on genes through, for example, DNA methylation and acetylation. The genome senses itself through its sensing genes and their proteins, and makes the necessary adjustments to sustain life, by correcting damage done or adopting new 'lifestyle' if damage is permanent but not lethal. Genes exposed to the outer environment are not expressed because of the influence of inhibitory factors from without, while the inner ones, shielded from such influences, are expressed. These sensors equally determine species body architecture. The master gene which determines the body plan binds many transcr...

Glycation is the non-enzymatic reaction of sugar with proteins, ribonucleic acids and fats. It occurs inside the body in the hyperglycemic state such as uncontrolled diabetes and impairs tissue function. It may occur locally or systemically in infections, that require high sugar, such as biofilms or in a high oxidative stress state. Externally, it occurs through cooking. Most of glucose damage in glycation occurs indirectly through the reactive dicarbonyl intermediate, formed from an auto-oxidation reaction of sugar, and occurs independent of direct molecular sugar glycation reaction. The dicarbonyl so formed cross-links and damages substances and structures, in tissues, organs or organelles, such as insulin, the endoplasmic reticulum, mitochondria and the cell membrane--and causes stresses. Glycation affects all tissues. The more reactive advanced end products of glycoxidation or [indirectly] glycation(AGEs), which are more powerful electrophiles than the initial dicarbonyls thems...

The p53, a protein that assists in the cell cycle arrest, takes the cell out of the cycle for autophagy and repairs, or self-destruction by apoptosis. The eventual viable cell then re-enters the cycle. The p53 gene is a potent anti-oncogene. When mutated, the cell will continue to carry out cell-cycling, unabated, and replication will continue--including of the telomere repeats-- as normal. There are isoforms of p53 involved, which sense the need for either apoptosis, or autophagy and repairs. Autophagy is anti-inflammatory as the cell is kept viable, shows no signs of distress(damage), safe, perhaps, for some cell shrinking(due to self-cannibalization of up to 50%)-- thus, there is no need to call for inflammatory cells. Equally, autophagy disposes of the inflammasome. Conversely, inflammation prevents autophagy, hence the need to reduce inflammation to promote the more useful and desirable phagocytosis, since autophagy disposes of intracellular pathogens and debris. Some intra...

One of the greatest challenges of our times is the complete eradication of infections from the body. Although acute infections have been taken care of, more or less, with antibiotics, the usage of this class of drugs, unfortunately, has promoted the emergence of persistent, chronic infections, in addition to the classical conferment of drug resistance. Biofilms are slime, formed in response to 'environmental' stress of various types, such as the immune system, nutritional stress, antibiotics or other toxicants, as a means to survival. They are composed of a self-assembled extracellular matrix of microbial polymeric carbohydrates, proteins, ribonucleic acid(DNA), fats, in addition to host proteins like fibrin, as well as minerals, and the pathogen. In addition, lipase is secreted, and it helps launch channels(porins) in the host membrane. Biofilms are tough to break or for the immune system and antibiotics to penetrate, hence the difficulty to treat infections in the plaqu...

Ebola virus shares a common toxic glycoprotein with some other viruses like the Indiana virus. This means a person previously infected with either virus becomes immune, at least partially, to subsequent Ebola or Indiana virus infection( having had an infection provides a better form of protection or 'vaccination'). Even a small contact with contaminated body fluid(blood, saliva, semen vaginal fluid etc), is able to result in an infection--viruses are tiny particles that easily penetrate tissues. It takes a couple of weeks for an infected person to develop signs and symptoms. This is incubation period, during which viral proteins are veing made, preparing the virus for subsequent multiplication and in anticipation of spread throughout the body. At this point in time, the person's fluid is highly contaminating and infecting, due to the high viral titre or load present therein. In the body, the Ebola virus particularly infects the white blood cell type called the monoc...