Inflammation & Autoimmunity
AIC in a Nutshell
AIC (Antiorbital Ionic Calcium) is the only true ionic calcium delivery system that provides calcium in free ionic state, which is the only physiologically active form of calcium in our body. Normally, calcium from diet and supplements enters our body in the protein-bound form and therefore, cannot trigger the same physiological responses as AIC. Resolving calcium deficiency better than protein-bound calcium, AIC triggers ionic-calcium-sensitive physiological responses that counteract the root cause of diseases and brings natural healing reactions of our body from cellular to the systemic level.
What is Inflammation and Inflammatory Disease?
Inflammation is the body’s normal response to illness and infection. But sometimes inflammation can be misdirected and triggers our own immune system to attack healthy tissue instead, causing inflammatory diseases such as Rheumatoid arthritis where our immune system attacks the body’s own healthy tissues. Inflammatory diseases include a vast array of disorders and conditions that are characterized by inflammation. Examples include allergy, asthma, autoimmune diseases, celiac disease, glomerulonephritis, hepatitis, inflammatory bowel disease, preperfusion injury, and transplant rejection.
Symptoms of inflammatory disease
People may feel flu-like symptoms with inflammation, such as headache, chills and muscle stiffness. The symptoms depend on where the inflammation is located and can include:
Redness and swelling in the affected area
Joint pain and joint stiffness
Loss of function and movement in the affected area
Prescription Drugs for Inflammation
Nonsteroidal anti-inflammatory drugs (NSAIDs) are medicines you can take for pain relief. They are often sold over-the-counter (OTC). This means you can buy them without a prescription from your doctor. Some common brand names are Advil, Motrin, or Aleve. But these medicines are available by prescription, as well.
NSAIDs stop a certain kind of enzyme in your body from working. These are called cyclooxygenase enzymes (also called COX enzymes). COX enzymes speed up your body’s production of hormone-like substances called prostaglandins. Prostaglandins irritate your nerve endings and cause you to feel pain. They are also part of the system that helps your body control its temperature.
By reducing the level of prostaglandins in your body, NSAIDs help relieve pain from conditions like arthritis. They also help reduce inflammation (swelling), lower fevers, and prevent blood from clotting.
There are 2 classes of prescription NSAIDs: traditional and COX-2 inhibitors.
You have 2 types of COX enzymes in your body: COX-1 and COX-2. Researchers believe that one of the jobs of COX-1 enzymes is to help protect your stomach lining. The COX-2 enzyme doesn’t play a role in protecting your stomach.
Traditional NSAIDs stop both COX-1 and COX- 2 enzymes from doing their jobs. When COX-1 enzymes are blocked, pain and inflammation is reduced. But the protective lining of your stomach is also reduced. This can cause problems such as upset stomach, ulcers, bloating, and bleeding in your stomach and intestines.
COX-2 inhibitors only stop COX-2 enzymes from working. The COX-2 enzyme doesn’t help to protect your stomach. So COX-2 inhibitors may be less likely to irritate your stomach or intestines.
Side Effects of NSAIDS
People who take NSAIDs increase their risk of developing severe bleeding in their stomachs. They may also be at risk for heart attacks and strokes. These risks get worse if they take prescription-strength higher doses. It also gets worse if they take these medicines for a long period of time. Common side effects of prescription NSAIDs may include: dizziness, headache, nausea, diarrhea, excess gas, constipation, extreme weakness or fatigue, dry mouth.
Serious, but rare, side effects of prescription NSAIDs may include allergic reaction. This could include difficulty breathing, hives, and swelling of the lips, tongue, or face. Also reported are : Muscle cramps, numbness, or tingling, Rapid weight gain, black, bloody, or tarry stools, bloody urine or bloody vomit, decreased hearing or ringing in the ears (also called tinnitus), Jaundice (the yellowing of the skin and the whites of the eyes), abdominal cramping, heartburn, indigestion.
In addition to the side effects listed above, people taking a COX-2 inhibitor may be at risk for: Swelling or water retention, skin rash or itching, unusual bruising or bleeding, and difficulty sleeping (insomnia).
Prescription Drugs for Rheumatoid Arthritis (an autoimmune disease)
DMARDs can often slow or stop the progression of RA by interrupting the immune process that promotes inflammation. However, because DMARDs target the immune system, they also can weaken the immune system’s ability to fight infections. This means you must do regular blood tests to make sure the drug is not hurting blood cells or certain organs such as your liver, lungs, or kidneys.
These are the main types of RA medications:
Disease-Modifying Anti-Rheumatic Drugs (DMARDs), Biologic response modifiers (a type of DMARD)
Glucocorticoids, Nonsteroidal Anti-inflammatory Medications (NSAIDs)
Analgesics (Pain Killers)
Many DMARDs have serious side effects such as seizures, headaches, hair loss, stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice, joint pain, bloody vomit, dry cough, shortness of breath, blood in your urine, swelling of feet, confusion, and little or no urinating
Acute inflammation is a short-term process occurring in response to tissue injury, usually appearing within minutes or hours. It is characterized by five cardinal signs: pain, redness, immobility (loss of function), swelling and heat.
Inflammation is part of the body’s defense mechanism. It is the process by which the immune system recognizes and removes harmful and foreign stimuli and begins the healing process. Inflammation can be either acute or chronic.
Acute Inflammation
Tissue damage due to trauma, microbial invasion, or noxious compounds can induce acute inflammation. It starts rapidly, becomes severe in a short time, and symptoms may last for a few days for example cellulitis or acute pneumonia. Subacute inflammation is the period between acute and chronic inflammation and may last 2 to 6 weeks.
Chronic Inflammation
Chronic inflammation is also referred to as slow, long-term inflammation lasting for prolonged periods of several months to years. Generally, the extent and effects of chronic inflammation vary with the cause of the injury and the ability of the body to repair and overcome the damage.
Dangers of Chronic Inflammation
Chronic inflammation can result from the following:
1. Failure of eliminating the agent causing an acute inflammation such as infectious organisms including Mycobacterium tuberculosis, protozoa, fungi, and other parasites that can resist host defenses and remain in the tissue for an extended period.
2. Exposure to a low level of a particular irritant or foreign material that cannot be eliminated by enzymatic breakdown or phagocytosis in the body including substances or industrial chemicals that can be inhaled over a long period, for example, silica dust.
3. An autoimmune disorder in which the immune system recognizes the normal component of the body as a foreign antigen, and attacks healthy tissue giving rise to diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE).
4. A defect in the cells responsible for mediating inflammation leading to persistent or recurrent inflammation, such as auto-inflammatory disorders (Familial Mediterranean Fever).
5. Recurrent episodes of acute inflammation. However, in some cases, chronic inflammation is an independent response and not a sequel to acute inflammation for example diseases such as tuberculosis and rheumatoid arthritis.
6. Inflammatory and biochemical inducers are causing oxidative stress and mitochondrial dysfunction such as increased production of free radical molecules, advanced glycation end products (AGEs), uric acid (urate) crystals, oxidized lipoproteins, homocysteine, and others.
Prescriptions for Chronic Inflammations
Conventional Drugs that Combat Chronic Inflammation
Metformin is commonly used in the treatment of type II diabetic patients with dyslipidemia and low-grade inflammation. The anti-inflammatory activity of metformin is evident by reductions in circulating TNF-alpha, IL-1beta, CRP, and fibrinogen in these patients.
Statins are anti-inflammatory as they reduce multiple circulating and cellular biomediators of inflammation. This pleiotropic effect appears to contribute in part to the reduction in cardiovascular events.
Non-steroidal anti-inflammatory drugs (NSAIDs) like naproxen, ibuprofen, and aspirin acts by inhibiting an enzyme cyclooxygenase (COX) that contributes to inflammation and are mostly used to alleviate the pain caused by inflammation in patients with arthritis.
Corticosteroids also prevent several mechanisms involved in inflammation. Glucocorticoids are prescribed for several inflammatory conditions including inflammatory arthritis, systemic lupus, sarcoidosis, and asthma.
Herbal supplements like ginger, turmeric, cannabis, hyssop, and Harpagophytum procumbens are shown to have anti-inflammatory properties however one should always consult with a doctor before their use and caution should be taken for using some herbs like hyssop and cannabis.
Startling Statistics of Chronic Inflammation Pathology
Chronic inflammatory diseases are the most significant cause of death in the world. The World Health Organization (WHO) ranks chronic diseases as the greatest threat to human health. The prevalence of diseases associated with chronic inflammation is anticipated to increase persistently for the next 30 years in the United States.
In 2000, nearly 125 million Americans were living with chronic conditions and 61 million (21%) had more than one. In recent estimates by Rand Corporation, in 2014 nearly 60% of Americans had at least one chronic condition, 42% had more than one, and 12% of adults had 5 or more chronic conditions. Worldwide, 3 of 5 people die due to chronic inflammatory diseases like stroke, chronic respiratory diseases, heart disorders, cancer, obesity, and diabetes. The prevalence of some specific chronic inflammation-mediated diseases are as follows:
Diabetes: According to the American Diabetes Association, 30.3 million people, or 9.4% of the American population, had diabetes in 2015 and it was the 7th leading cause of death in the United States.
Cardiovascular diseases: In line with 2017 updated report from the American Heart Association, cardiovascular diseases (CVDs) accounts for 1 out of every three deaths or approximately 800,000 deaths in the United States. Globally, CVD accounts for 31% of all deaths, and coronary heart disease (CHD) accounts for most deaths due to CVD, followed by stroke (1 of 20 deaths in the United States) and heart failure.
Arthritis and Joint Diseases: These affect approximately 350 million people worldwide and nearly 43 million people in the United States or almost 20% of the population. This number is expected to exceed 60 million by 2020. Nearly, 2.1 million Americans suffer from rheumatoid arthritis.
Allergies: These rank among the sixth leading cause of chronic human diseases in the United States and affect more than 50 million Americans each year. Asthma affects more than 24 million people in the United States including more than 6 million children. In 2015, 8.2% of adults and 8.4% of children were diagnosed with hay fever.
Chronic Obstructive Pulmonary Disease (COPD): The third most common cause of death in the United States in 2014, and nearly 15.7 million Americans (6.4%) were reported to have been diagnosed with COPD.
Understanding the Pathophysiology of Chronic Inflammation
Most of the features of acute inflammation continue as the inflammation becomes chronic, including the expansion of blood vessels (vasodilation), increase in blood flow, capillary permeability, and migration of neutrophils into the infected tissue through the capillary wall (diapedesis). However, the composition of the white blood cells changes soon, and the macrophages and lymphocytes begin to replace short-lived neutrophils. Thus the hallmarks of chronic inflammation are the infiltration of the primary inflammatory cells such as macrophages, lymphocytes, and plasma cells in the tissue site, producing inflammatory cytokines, growth factors, enzymes and hence contributing to the progression of tissue damage and secondary repair including fibrosis and granuloma formation, etc.
In response to foreign or self-antigens, the tissue immune cells such as macrophages and dendritic cells release cytokines such as IL-1 and TNF-α. These cytokines induce the injury-site-endothelial cells to release Selectins and Integrins which stimulate chemotaxis and diapedesis of the circulating leukocytes. In addition to the recruitment of leukocytes, the tissue macrophages, and dendritic cells also play a role in the clearing of the antigen by phagocytosis, the release of cytokines, and serving as antigen-presenting-cells to lymphocytes. Once the circulating leukocytes enter the local injury site, they are activated by various cytokines and chemokines secreted by the macrophages and dendritic cells. On activation, the leukocytes further release cytokines and mediators of inflammation. Neutrophils are the initial cells and most predominant in the acute phase of inflammation. Neutrophils contain granules rich with lysozyme, matrix metalloproteinases, myeloperoxidase which are released on the foreign or self-antigen leading to its destruction. Neutrophils also destroy the antigen by phagocytosis, the release of reactive oxygen species and cytokines such as IL-1, IL-6, and TNF-α
Lymphocytes including T-lymphocytes and B-lymphocytes are the next line of defense, and they play a crucial role in mediating inflammation by several complex mechanisms including secreting of cytokines, costimulation of lymphocytes, and production of antibodies and immune complexes. Circulating platelets can also play a role in inflammation by platelet aggregation, thrombus formation, and degranulation releasing chemokines and inflammatory mediators.
Types of Chronic Inflammation
Nonspecific proliferative: Characterized by the presence of non-specific granulation tissue formed by infiltration of mononuclear cells (lymphocytes, macrophages, plasma cells) and proliferation of fibroblasts, connective tissue, vessels, and epithelial cells, for example, an inflammatory polyp-like nasal or cervical polyp and lung abscess.
Granulomatous inflammation: A specific type of chronic inflammation characterized by the presence of distinct nodular lesions or granulomas formed with an aggregation of activated macrophages or its derived cell called epithelioid cells usually surrounded by lymphocytes. The macrophages or epithelioid cells inside the granulomas often coalesce to form Langhans or giant cells such as foreign body, Aschoff, Reed-Sternberg, and Tumor giant cells. There are two types:
Granuloma formed due to foreign body or T-cell mediated immune response is termed as foreign body granuloma, for example, silicosis.
Granuloma formed due to chronic infection is termed as infectious granuloma, for example, tuberculosis and leprosy.
Research: Cytokine-induced Bone Resorption Aggravates Inflammation
“The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and magnesium by bone resorption may sustain and intensify the inflammatory response… Thus, extracellular calcium, by means of the parathyroid calcium-sensing receptor, is able to modulate inflammation-mediated resorption.”
AIC therapy, therefore, by reversing cytokine-mediated resorption which sustains and intensifies inflammatory response, helps to reduce inflammations.
AIC Stimulates Stem Cells
Cartilage formation requires a concerted action of numerous intracellular signal transduction molecules, many of which are sensitive to the changes of intracellular Ca2+ concentration.
AIC restores calcium homeostasis which helps to trigger dormant stem cells to work diligently in repairing damaged cartilage and joints.
AIC Clears Calcium Deposits
When we start losing bone mass with aging, CPP and apatite crystal calcification happens in joints that damages joints.
AIC dissolves joint calcification and navigates calcium back to the bone. AIC clears bone spurs and helps remodel damaged joints back to its healthy form.
AIC Corrects Immune Response
Cellular damage caused by oxidative stress and disrupted signalling damage cellular membrane integrity and invites unwanted attention of T cells as it often happens around joints.
By reducing cellular oxidative stress and restoring proper calcium signalling, cells undergo repairing process that no longer attract autoimmune response.
AIC Eases Pain & Inflammations
Over-acidity in the body can increase inflammation and aggravate arthritis while alkalizing can relieve inflammation and pain associated with it.
Ionic calcium is one of the best alkalizing agent that can reduce inflammation and pain. AIC also dissolves calcification around joints that also contributes to pain and inflammations.
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