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C reactive Protein Test

C reactive protein is an acute phase reactant produced by the liver as an inflammatory response because of an infection. C reactive protein determination detects the presence of inflammation in the body. C-reactive protein values are very significant in determining the possibilities of long term diseases such as myocardial infarction, neoplastic proliferation and also some inflammatory diseases caused due to infection. C-reactive protein is also considered as the scavenger protein. It binds to many microorganisms in facilitating the process of cell mediated cytotoxicity and also phagocytosis.


C reactive protein test is advised to patients who undergo surgeries pertaining to both general and transplantation categories. It enables in determining the underlying causes of graft rejection. The general CRP determination is of less significance as the values obtained may not describe the underlying health conditions in a specific way. This diagnostic obligation pertaining to the exact values of CRP is eliminated with the introduction of highly sensitive C-reactive protein test (HsCRP).


Principle of the Hs-CRP test

Highly sensitive CRP test is ordered especially in the diagnosis of cardiovascular disease. Hs-CRP test is done using the enzyme linked immunosorbent assay (ELISA). The procedure involves the use of a unique monoclonal antibody which is targeted against a distinct antigenic determinant on the CRP. The CRP molecules in the test sample are sandwiched between the monoclonal antibody which forms the solid phase for immobilization in the test and the enzyme linked antibodies.


Physiology and clinical manifestations

The CRP levels in the body significantly increase after 24 to 48 hours as a response to indicate the onset of tissue damage. These values may remain constant for a longer duration before they reach the normal values. The American Heart Association and the Center for Disease Control have determined the risk groups based on the CRP values. Patients with CRP value less than 1mg/L fall under the low risk groups and values ranging from 1 to 3 mg/L indicate the patients fall under average and high risk groups for cardio vascular disease.


The values of high sensitivity C reactive protein test are part of cardiovascular disease diagnosis. These values are further correlated with other important parameters such as cholesterol levels and glucose levels. Careful analysis is required to understand the history of the patient before the test. This analysis includes a previous history of smoking, infectious disease, alcoholism etc. The hsCRP level values vary if the patient has previously taken non steroidal anti inflammatory drugs. High sensitivity CRP ratios have exceptions in clinical conditions such as arthritis because of the high inflammatory response seen in these conditions. The values are not taken into consideration under these conditions. Coronary artery disease related conditions are predicted in healthy individuals through the hsCRP test.


This Hs CRP test serves as an effective marker in identifying the risk for coronary artery related stroke or heart attack in a healthy individual. The hs-CRP test is also used in the detection of colon cancer and complications related to diabetes and obesity. The hs-CRP test is increasingly becoming an effective test in the pharmacological management of patients by the clinicians as it gives details for the precise use of statins and anti thrombotic medications. Research pertaining to the comparative ratio drawn between patients having high CRP values and low LDL (low density lipoproteins) values prove that these patients are at greater risk of developing cardiovascular disease. These studies conclude that the hs-CRP test is a significant marker in prediction of asymptomatic cardiovascular disease among healthy individuals. The hs-CRP test is also effective in the determination of HNF1A mutations which act as the precursor for the maturity onset diabetes of the young (MODY). This helps in the screening of unidentified diabetes.

Tau Brain Scans

The deadly disease Alzheimer's takes a terrible toll on not just memories but also lives of millions year on year. Although doctors use checklists of symptoms and signs to detect Alzheimer's, these methods are open to major variations in medical opinion about a single patient. There is a danger of Alzheimer's disease - AD - being confused with any other dementia or common declining intellectual disabilities.


Sometimes, memory loss need not be the first symptom of Alzheimer's and it could be behavioral or language changes or difficulty in everyday activities. Hence, doctors treating Alzheimer are always left to face uncertainty in trying to diagnose the disease in the living, and only an autopsy can confirm the disease for certain.

A pioneering brain image - Tau brain imaging - can detect the build-up of destructive proteins linked to Alzheimer's. This is the beginning of diagnosing the condition and testing of new drugs. Reported in the journal Neuron, tau brain scan can identify living clumps of a protein called tau that is closely linked to the disease. With this new diagnosis, patients can be helped early to make the most of their remaining life span. This definitive diagnosis can tell Alzheimer's disease apart from other disorders.


To understand this, it is relevant to know that Alzheimer's patients lose their brain's nerve fibers and there is an abnormal buildup of protein that damages nerve cells. Patients who begin with mild memory loss soon worsen to become restless, anxious, confused and moody. Patients lose their ability to talk or care for themselves in the final stages.


Tauopathies are a set of neuro-degenerative diseases associated with phosphorylated tau protein aggregation in the human brain. In Alzheimer's, tau protein is deposited within the neurons as neurofibrillary tangles. The German psychiatrist and later Neuro pathologist Dr. Alois Alzheimer was the first to describe this disease as pre senile dementia.

It is the associated protein tau that causes the tangles to aggregate in an insoluble form. The tau protein is referred to as 'PHF' or paired helical filaments. There are other conditions as well in which such neurofibrillary tangles are observed and these include progressive supranuclear palsy, chronic traumatic encephalopathy, Parkinson-dementia complex, ganglioglioma, meningioangiomatosis and tuberus sclerosis among others. These non-Alzheimer's tauopathies are grouped as Pick's complex.


A protein called tau (τ) is very closely linked to Alzheimer's and tangles of tau are thought to be one way in which the brain cells are killed. Researchers have developed a chemical that could bind to tau and then be detected during a brain scan. This was tested on mice and people and it showed that suspected Alzheimer's could be revealed by this technology that could detect tau.

Dr Makato Higuchi, National Institute of Radiological Sciences, Japan says that this emission tomography image of tau accumulation provides robust information on brain regions and also risk for tau-induced neuronal death. Although this research is at an early stage, it could eventually lead to identifying Alzheimer's.

As another Alzheimer's expert says "Tau can be compared to railroad ties that stabilize a train truck that brain cells use to transport food, messages and other vital cargo throughout neurons. In Alzheimer's, changes in tau protein causes the tracks to become unstable in neurons of the hippocampus, the center of memory. Abnormal tau spreads from cell to cell, disseminating pathological tau in the brain cortex".


While researchers have already tried time-tested medical imaging techniques to detect this disease, and while magnetic resonance imaging and computed tomography scan only rule out other disorders, there is no positive detection tool for Alzheimer's. Tau imaging highlights a new method for detecting tau, which would be a key player in both Alzheimer's and frontotemperal dementia in the living brain. The tau scan is capable of visualizing the protein inside the brain and is important for assessing whether treatments in clinical trials are hitting the target.

If the tau scan is shown to be effective, then it could become a potential aid for providing people with accurate diagnosis for monitoring the disease progression. The new focus for Alzheimer's treatment is halting the toxic tau.


A set of researchers at the Mayo Clinic in the US were able to look at the evolution of tau using neuro pathologic measures. Just like one could identify the changing seasons by looking at the rings of a tree, and the aging of the tree by viewing the cross section, studying the different stages of Alzheimer's gives a perspective of the cognitive impact of a wide range of amyloids and tau severity. At the Mayo brain bank, a collection of thousands of post mortem brains have allowed to understand changes in tau and amyloid that occur over a period of time.

There is an estimated 3 to 4 million people in the US with some form of Alzheimer's and there is a tendency for the number to increase over the years. Therefore, a good diagnostic tool is a must. Tau imaging represents significant advancement in the field and it is hoped that combined tau and amyloid positive PET scans may in the future help researchers get closer to an affirmative diagnosis of Alzheimer's disease.



Myoglobin

Myoglobin is one of the most important proteins in the human body. It is found in smooth and skeletal muscle tissue; where it binds oxygen and provides energy to power muscular contractions. It is an iron-oxygen binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is found in skeletal and cardiac muscles. It is a Hemeprotein that facilitates intracellular oxygen storage and transcellular diffusion of oxygen. Myoglobin's affinity for oxygen is higher than hemoglobin. And unlike hemoglobin which is found in the red blood cells, Myoglobin is found in muscle tissues. Myoglobin, together with the cytochromes, is responsible for the red-brown color of muscles.


In 1958, scientists Max Perutz and John Kendrew determined the 3D structure of Myoglobin by X-ray crystallography and interestingly, Myoglobin is the first protein to have its three-dimensional structure determined. In 1962, both these eminent scientists shared the Nobel prize for constructing a three-dimensional model of crystalline sperm-whale Myoglobin utilizing the technique of X-ray diffraction.


Myoglobin structure and functions


  • Myoglobin transports or stores oxygen in muscles. Unlike other proteins, myoglobin is able to bind with oxygen because it contains Heme,a metal-containing prosthetic group that allows it to bind to oxygen.

  • Myoglobin consists of a single polypeptide chain

  • Myoglobin occurs as a monomeric heme protein

  • Myoglobin contains only one heme binding sub-unit surrounded by a globular protein, containing eight alpha-helical and six non helical segments, made up of 153 amino acids.

  • During the period of oxygen deprivation, oxymyoglobin releases its bound oxygen for metabolic purposes.

Myoglobin test results

For Men: 10 - 95 ng/ml (onset: 1-3 hrs, peak: 6-10 hrs, return to normal: 12-24 hrs)

For Women: 10 - 65 ng/ml (onset: 1-3 hrs, peak: 6-10 hrs, return to normal: 12-24 hrs)


Myoglobin Test

Myoglobin serum test may be used detect muscle damage. Myoglobin is rapidly released after muscle damage, and thus can be a useful bio marker in the early phases of muscle injury. When heart or skeletal muscle is injured, Myoglobin is released into the blood. When the damage is severe, Myoglobin levels in the blood shoot up within few hours of damage.

Excess Myoglobin in the blood is filtered by kidneys and released into the urine. And thus, severe muscle damage followed by high amounts of Myoglobin in the serum and eventually in the urine may lead to renal failure. Myoglobin levels are tested to identify the presence and timing of muscle damage. However, it cannot determine the location of muscle injury/damage. The Myoglobin blood test is also commonly used to identify a recent heart attack or acute myocardial infarction. Other sensitive markers like troponin are more commonly used today to detect heart conditions.


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Collection of Pages - Last revised Date: August 19, 2018