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Sunday, December 21, 2014

Recapitulate the Role of Troponin in Cardiac Muscle Contraction

At molecular level, striated muscle (Heart Muscle is striated) consists of myofibrils (A Protein), which are of two types-thick and thin myofilaments. A thick filament containing myosin and a thin filament consisting of 3 different proteins: actin, tropomyosin, and troponin.
Cardiac troponin (cTn) is itself a complex of 3 protein subunits: troponin T (cTnT), troponin I (cTnI), and troponin C (cTnC). Troponin T binds the troponin complex to tropomyosin. Troponin I inhibits actomyosin ATPase in relation to the calcium concentration. Troponin C, with its 4 binding sites for calcium, mediates calcium dependency.

In resting state, tropomyosin winds over to cover the binding sites on the actin; can be imagined like a cover that wind over the facets (where the myosin head would like to lock itself). Here, cTnT can be imagined as several nails that fix tropomyosin over the actin.
With release of calcium from the cytosol of muscle cells cTnC attaches 4 Ca+ to the 4 binding sites on it, in turn activates cTnI that lifts the inhibition of ATPase in the myosin head; myosin, after getting energy from hydrolysis of ATP, goes for conformational changes of its' head and crawls over the actin molecule, thereby contraction of muscle occurs.
In a over simplified way, it can be said that an activated troponin complex removes the tropomysin cover from the actin, thereby unblocks the binding sites for myosin. Myosin head crawls over the facets on the actin, and pulls the actin to cause a contraction of the myofibril.

English: This is a recropped image originally ...
English: This is a recropped image originally created by Hank van Helvete (Photo credit: Wikipedia)
In the cytosol, troponin T is found in both free and protein-bound forms. The unbound (free) pool of troponin T is the source of the troponin T released in the early stages of myocardial damage. Bound troponin T is released from the structural elements at a later stage, corresponding with the degradation of myofibrils that occurs in irreversible myocardial damage.
The most common cause of cardiac injury is myocardial ischemia, ie, acute myocardial infarction. Troponin T becomes elevated 2 to 4 hours after the onset of myocardial necrosis, and can remain elevated for up to 14 days.
Elevations in troponin T are also seen in patients with unstable angina. The finding of unstable angina and an elevated troponin T are known to have adverse short- and long-term prognoses, as well as a unique beneficial response to an invasive interventional strategy and treatment with the newer anti-platelet agents and low-molecular-weight heparin.
Useful For: cTnT and cTnI are useful for the exclusion of diagnosis of acute myocardial infarction. Monitoring of acute coronary syndromes and estimating prognosis. Possible utility in monitoring patients with non-ischemic causes of cardiac injury.

Sunday, October 19, 2014

An Overview on Ebola Virus Disease (EVD) Transmission

Ebola, name of a river in the Democratic Republic of Congo, in the bank of which people of a village were affected from a type of haemorrhagic fever in 1976, inadvertently got coined its' name with the disease that claimed many deaths. Simultaneously, another outbreak was also detected in Nzara, Sudan.

English: Ebola virus virion. Created by CDC mi...
English: Ebola virus virion. Created by CDC microbiologist Cynthia Goldsmith, this colorized transmission electron micrograph (TEM) revealed some of the ultrastructural morphology displayed by an Ebola virus virion. (Photo credit: Wikipedia)

The current outbreak in west Africa, starting in Guinea (first cases notified in March 2014), is the largest and most complex Ebola outbreak since the Ebola virus was first discovered in 1976.
The virus belongs to the family of Filoviridae that includes 3 genera:
  • Cuevavirus, 
  • Marburgvirus, and 
  • Ebolavirus.
There are 5 species that have been identified and named after the places of discoveries:
  • Zaire, 
  • Bundibugyo, 
  • Sudan, 
  • Reston and 
  • Taï Forest;
The first 3, Bundibugyo ebolavirus, Zaire ebolavirus, and Sudan ebolavirus have been associated with large outbreaks in Africa. The virus causing the 2014 west African outbreak belongs to the Zaire species.
Unlike some other viruses, such as influenza or SARS, Ebola virus is not spread through the air, which has been questioned recently; there has been a theoretical possibility at least.
It is not spread by water or through mosquitoes or other insects. Ebola can be spread from person to person only while the infected person is displaying symptoms. The incubation period ranges from 2 to 21 days; in an average of 8 to 10 days.
It appears that the first victim of the current Ebola outbreak in West Africa was a 2-year old boy in South-eastern Guinea, possibility coming in contact with droppings from infected bats, died in December of 2013, followed by the deaths of several members of his family.
Human to human transmission may be possible coming direct contact with saliva, semen, sweat, tears, vomits, vaginal fluid, feces, blood and used belongings of the patient; through mucus membranes of eye and mouth; through broken skin.
The virus has been isolated from semen, saliva, tears, sweat, urine, vomits, vaginal fluid and faeces of convalescent EVD patients for several days, through RT-PCR (Reverse Transcription Polymerase Chain Reaction) test for RNA.
The maximum recorded persistence of Ebola virus RNA in the blood and other body fluids of convalescent EVD patients varies by fluid type. Across combined studies (each study did not examine the exact same fluid types at the same time points), Ebola virus RNA has been detected up to 101 days after symptom onset in semen, 33 days from vaginal swabs, 29 days from rectal, 23 days from urine, 22 days from conjunctival swabs, 21 days in blood, 15 days in breast milk, eight days in saliva, and six days on skin.
Though multiple studies have shown that Ebola virus can persist in semen for longer than in blood or other body fluids, sexual transmission of Ebola has not been definitively established.
EVD among healthcare personnel and other persons is associated with direct contact with infected persons (or the bodies of persons who have died from EVD) and direct contact with body fluids from EVD patients.
CDC infection control recommendations for U.S. hospitals, including recommendations for standard, contact, and droplet precautions for general care, reflect the established routes for human-to-human transmission of EVD and are based on data collected from previous EVD outbreaks in Africa in addition to experimental data.
Airborne transmission of EVD among humans has never been demonstrated in investigations that have described human-to-human transmission although hypothetical concerns about airborne transmission of EVD have been raised.
ZMapp, a combination of three monoclonal antibodies that bind to Ebola, has been used experimentally on a few patients, and it stopped the virus in animal trials. Blood transfusion from survivors are being tried and some positive results have been obtained.
Best of preventive nursing care (Barrier Nursing) is the key to prevent the spread of the disease.
Related articles

Sunday, September 14, 2014

Host of Bacteria in Fermented Dairy Products acting in conjunction with the Gut Bacteria take care of Gut and Body Health

Fermented dairy products like yogurt and cheese contain a number of genera of bacteria called probiotics having beneficial effect on human gut. They are  members of the genera Lactobacillus, Lactococcus, Leuconostoc, Enterococcus, Pediococcus, Streptococcus, Staphylococcus and bifidobacterium.
There are 100 trillion (1012) of microbes in the mammalian intestines. They live in the human gut and help in many ways; some of those are responsible for fermentation of resistant dietary fibers, which are otherwise indigestible by gut enzymes in human. Those are also called as commensals.
Adopted from PNAS

Some commensals are involved in the fermentation of dietary fibers in the colon leading to production of short chain fatty acids (SCFAs), 2-carbon to 5-carbon weak acids including acetate (C2), propionate (C3), butyrate (C4) and valerate (C5). Among the SCFAs, butyrate has received particular attention for its multiple beneficial effects from the intestinal tract to the peripheral tissues.
The most important butyrate producers appear to be Faecalibacterium prausnitzii, which belongs to the Clostridium leptum (or clostridial cluster IV) cluster, and Eubacterium rectale/Roseburia spp., which belong to the Clostridium coccoides (or clostridial cluster XIVa) cluster of firmicute bacteria.
Butyrates can be produced from lactate in gut by the microbiota. Lactic acid producing bacteria like Lactobacillus and bifidobacterium are found in fermented dairy products. Thus, a lower PH or an acidic environment in gut may be a better place for butyrate producing bacteria.
The SCFAs have anti-inflammatory effect in the gut. Though the exact mechanism has not been established, it is thought that the SCFA have immunomodulatory effects on colonic macrophages, which are important cell types responsible for inflammation.
It has been found out by the researchers that n-butyrate silences genes responsible for expression of pro-inflammatory mediators including Nos2, Il6, Il12a, and Il12b.
The host immune system must constantly maintain a balance between tolerance to commensals and immunity against pathogens to avoid unnecessary immune responses against otherwise harmless bacteria in the intestine.
Adopted from PNAS

In a study, researchers have demonstrated that n-butyrate regulates macrophage function through the inhibition of Histone Deacylases (HDACs). HDACs keep genes in compact form, preventing uncoiling; when inhibited, there occurs uncoiling of chromatin, a step that proceeds for gene expression (Transcription).
Butyrate induced histone acylation results in production of factors that down-regulate certain gene expression that are harmful; whereas up-regulate function of another set of genes that have protective effect.
The precise mechanism proposed is the transcriptional up-regulation of detoxifying enzymes, such as glutathione-S-transferase (GST). The modulation of the GST gene may protect cells from genotoxic carcinogens, such as H2O2 and 4-hydroxynonenal (HNE). There occurs suppression of nuclear factor κB (NFkB) activation, the inhibition of interferon γ production and the upregulation of peroxisome proliferator-activated receptor γ (PPARγ).
As a result, intestinal macrophages reduce production of pro-inflammatory mediators such as NO, IL-6, and IL-12. Butyrate induces anergy in intestinal macrophages making immune system hypo-responsive to the beneficial, n-butyrateproducing bacteria.
In the absence of these beneficial bacteria, lamina propria macrophages remodel the intestinal microbial communities by eliminating unwanted populations of bacteria through the production of pro-inflammatory mediators until the optimal microbial balance is re-achieved and the levels of n-butyrate return to the desired concentrations.
Misregulated responses can lead to inflammatory bowel diseases such as ulcerative colitis or Crohns disease.
Intervention studies in patients with ulcerative colitis (UC) suggested that the luminal administration of butyrate or stimulation of luminal butyrate production by the ingestion of dietary fibers results in an amelioration of the inflammation and symptoms.
Hallert et al. instructed 22 patients with quiescent UC to add 20 g of dietary fibers to their daily diet. A total of 4 weeks of this treatment resulted in a significant increase of fecal butyrate concentration and in a significant improvement of abdominal symptoms.
Vernia et al. in a double-blind, placebo-controlled multicenter trial, treated 51 patients with active distal UC with rectal enemas containing either 5-aminosalicylic acid (5-ASA) or 5-ASA plus sodium butyrate (80 mM, twice a day). The combined treatment with topical 5-ASA plus sodium butyrate resulted in a significant improvement of the disease activity score compared to that observed in patients treated with 5-ASA alone.
Fermented dairy products (low fat) along with adequate amount of dietary fiber (Resistant, available from whole wheat, green banana, onion, peas and beans etc.) may benefit gut/body health acting together.


Thursday, September 4, 2014

Spinach Extract can help in Increasing Weight Loss

Spinach has long been considered as a companion of very healthy diet. Now, researchers from Lund University in Sweden have proved that taking green extract of spinach increases weight loss and decreases food craving.
The principal ingredient is membrane called thylakoids contained in the chloroplast that imparts the green colour to the leaves. This thylakoid can be extracted by crushing the leaves and centrifuging it.

A vectorised version of File:Chloroplast-new.j...
A vectorised version of File:Chloroplast-new.jpg. A diagram showing the simple structure of a chloroplast (Photo credit: Wikipedia)

It is fund that if it is taken prior to the breakfast there is a decreases hedonic hunger up to 95% -- and increase in weight loss up to 43%.
This happens because of the feeling of satiety and suppression of hedonic hunger, vs homeostatic hunger that deals with our basic energy needs.
Modern processed food is broken down so quickly that the hormones in the intestines that send satiety signals to the brain and suppress cravings cannot keep up.
The green leaf membranes slow down the digestion process, giving the intestinal hormones time to be released and communicate to the brain that we are satisfied.
A prolongation of fat digestion and concomitant release of satiety hormones and reduction of hunger peptides cause the effect.
Thylakoids bind to the pancreatic lipase-colipase complex resulting in the reduction of lipolysis (fat breakdown) by preventing contact of the enzyme complex to the lipid substrate.
Sooner or later the thylakoids themselves are degraded by proteases and the body will eventually take up the fat. However, by this time the satiety induced by the prolongation of the digestion process results in a net reduction of food intake.
Thylaloids contain phospholipids and proteins. The main components of the thylakoids that are responsible for the reduction of lipolysis are the hydrophobic transmembrane polypeptide chains of the protein complexes of the membrane.
Thylakoids are the place where photosynthesis occurs in the chloroplasts. They are responsible for the light reaction whereby light is captured and its energy converted to chemical energy in the form of ATP and NADPH concomitant with the development of oxygen.

Thylakoid disc with embedded and associated pr...
Thylakoid disc with embedded and associated proteins (Photo credit: Wikipedia)

The thylakoids are made up of over a hundred of membrane proteins which together with pigments, chlorophyll and carotenoids, and membrane lipids, mainly galactolipids, form a highly complex membrane system that not only carries out electron transport and ATP synthesis but also harvest light, with the help of the pigments in a very efficient way.
In addition the thylakoids have a very ingenious system of repair and antioxidants for protection against damage caused by light and oxidative stress. Thylakoids are probably the most complicated of biological membranes. They are the most abundant of all biological membranes on earth.

Monday, August 11, 2014

More Natural Light in Workplace contributes to Good Sleep and Healthy Life

Sleep plays an important role in synchronizing body and mind, maintaining the body’s circadian clock that up keeps correct rhythm.
Inadequate sleep and sleep deprivation contribute to;
  1. Heart disease,
  2. Diabetes,
  3. Depression,
  4. Accidents,
  5. Impaired cognition,
  6. Irritability and
  7. A poor quality of life.
While normal changes due to ageing interfere with the quality of sleep, some disease conditions and medications used by older adults compromise sleep patterns. Now, researchers have come out with evidence that light in work environment also contribute positively to the sleep pattern.

A study published in The Journal of Sleep Medicine authored by Mohamed Boubekri, Ivy N. Cheung, Kathryn J. Reid, Chia-Hui Wang, Phyllis C. Zee, conclude that  exposure to light, during the day, particularly in the morning, is beneficial to health via its effects on mood, alertness and metabolism.
Employees with windows in the workplace received 173 percent more white light exposure during work hours and slept an average of 46 minutes more per night than employees who did not have the natural light exposure in the workplace, the study shows.
There also was a trend for workers in offices with windows to have more physical activity than those without windows. The quality of sleep was measured by Pittsburgh Sleep Quality Index (PSQI) that differentiates “poor” from “good” sleep by measuring seven domains: subjective sleep quality, sleep latency, sleep duration,habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction over the last month.
The client self rates each of these seven areas of sleep. Scoring of the answers is based on a 0 to 3 scale, whereby 3 reflects the negative extreme on the Likert Scale. A global sum of “5”or greater indicates a “poor” sleeper.
Good design of house and office with adequate number of windows not only saves power, but also allows the users to enjoy a healthy life.

Sunday, July 13, 2014

Flatus Gas (H2S) may have Protective Effect on Progression of Various Diseases in Human

Hydrogen sulphide (H2S) is a colourless gas with an odour of rotten eggs, long familiar to the students who worked in Chemistry Laboratories.
It is increasingly coming into light that, in fact, H2S can prevent cell damage in human from the noxious effect following myocardial infarction, brain stroke, traumatic brain injury, diabetes, atherosclerosis, Alzheimer’s disease and kidney injury etc.. This gas, in minute quantities, which is yet to be quantified, may actually protect mitochondria the power house of body. 
Photo Credit: Mail Online Health

It is produced in the human gut, mostly in colon by fermentation of food from bacterial action. Cystathioneine-lyase (CSE) and cystathionine-synthase are the two enzymes that regulate H2S levels in mammals (including humans).
CSE is found in the liver and vascular smooth muscle cells, but cystathioinine-synthase produces H2S in the brain.
Garlic can be transformed into H2S by enzymatic action in the body, so that some of its claimed medicinal properties can be traced to H2S.
It has been seen to be an important mediator of gastrointestinal (GI) mucosal defence and contributes significantly to repair of damage and resolution of inflammation. Synthesis of H2S increases markedly after mucosal injury, and inhibition of H2S in such circumstances leads to delayed healing and exacerbated inflammation.
The beneficial effects of H2S may be attributable to its ability to elevate mucosal blood flow, prevent leukocyte-endothelial adhesion, reduce oxidative stress, and stimulate angiogenesis.
Thus novel H2S -based therapies have been shown to be effective anti-inflammatories that can promote the resolution of inflammation and accelerate the healing of GI ulcers. Encouraging results have already been seen experimentally with a mesalamine derivative and with H2S -releasing derivatives of non-steroidal anti-inflammatory drugs.
Researchers at Johns Hopkins University, in Maryland, found that the H2S gas is produced in the cells lining blood vessels by CSE that relaxes the blood vessels, may have a role in regulating blood pressure.
In neurotoxin-induced Parkinson’s disease animal models, it has been seen that sodium hydrogen sulphate (NaHS), an H2S donor, reversed dopaminergic neuron loss via its anti-oxidant, anti-inflammatory and anti-apoptotic effects.
It has been found that the characteristic memory deficiency in Alzheimer’s disease (AD) may be related to reduced H2S and administration of NaHS could provide a therapeutic approach for AD.  Sufficient evidence has accumulated in support of H2S acting as a signalling molecule in the mammalian Central Nervous System (CNS).
Its beneficial effect in Alzheimer’s disease in animal models has also been substantiated. It has been seen that NaHS inhibited formation of amyloid β , which is a major component of the neuritic plaques by down-regulation of β-amyloid precursor protein (APP) expression and suppression of the activity of β-secretase, a β-site APP cleaving enzyme 1 (BACE1).
Abnormal accumulation of tau protein, a neuronal microtubule-associated protein that causes paired helical fragments (PHF) in Alzheimer’s disease is inhibited by NaHS through hyperphosphorylation, polymerization and aggregation.
Hydrogen sulfide has recently been found decreased in chronic kidney disease. A hydrogen sulfide donor (sodium hydrogen sulfide) inhibited renal fibrosis by attenuating the production of collagen, extracellular matrix, and the expression of α-smooth muscle actin.
At the same time, the infiltration of macrophages and the expression of inflammatory cytokines including interleukin-1β, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in the kidney were also decreased.
In cultured kidney fibroblasts, a hydrogen sulfide donor inhibited the cell proliferation by reducing DNA synthesis and down-regulating the expressions of proliferation-related proteins including proliferating cell nuclear antigen and c-Myc.
Further, the hydrogen sulphide donor blocked the differentiation of quiescent renal fibroblasts to myofibroblasts by inhibiting the transforming growth factor-β1-Smad and mitogen-activated protein kinase signaling pathways. Thus, low doses of hydrogen sulphide or its releasing compounds may have therapeutic potentials in treating chronic kidney disease.
Experiments with mice have shown that H2S can reduce their ability to metabolize oxygen, reducing their heart rate and breathing rate, lowering their body temperature, and creating a state of deep hibernation. By flushing with air, the mice can be restored to normal without apparent behavioural effects.
The possibility of using H2S in heart surgery or treating badly injured soldiers is being studied. By studying roundworms (C. elegans) it has been shown that 50 parts per million of H2S can extend their lives by 70 percent. This "fountain of youth" phenomenon seems to be connected to the gene SIR-2, which had previously been related to life span regulation. 
These preliminary findings are very exciting and may lead to medical advances. H2S appears to be another example of a "gasotransmitter" such as the hormone NO. Researchers speculates that H2S may be involved in the hibernation of certain animals.
Now researchers have come up with a new compound named AP39 to assist the body in producing just the right amount of hydrogen sulphide. 
They believe that it will help prevent or reverse mitochondrial damage, which is a key strategy in treating conditions such as stroke, heart failure, diabetes, arthritis, dementia and ageing.

The past few years demonstrated its role in many biological systems and it is becoming increasingly clear that H2S is likely to join nitric oxide (NO) and carbon monoxide (CO) as a major player in mammalian a cardioprotectant for treating ischaemic heart diseases and heart failure.
H2S treatment represents a novel therapeutic strategy to prevent acute lung injury induced by high tidal volume (HVT) ventilation. Moreover, it is pivotally involved in the control of important functions in the central nervous system (CNS).
H2S facilitates the induction of hippocampal long-term potentiation by enhancing the activity of N-methyl D, L-aspartate (NMDA) receptors. H2S induces Ca2+influx in astrocytes that propagates to the surrounding astrocytes as Ca2+ waves.
In stroke, H2S appears to act as a mediator of ischemic injuries and thus inhibition of its production has been suggested to be a potential treatment approach in stroke therapy.
Cerebral oedema has been reported to be one of the major factors leading to the high mortality and morbidity associated with patients with traumatic brain injury (TBI).
 A recent study interestingly showed that H2S at a low concentration significantly attenuated the injury in a mild focal cerebral ischemia rat model.
It was observed that low concentration of H2S is neuro-protective, whereas higher concentrations of H2S have been shown to magnify cerebral damage.
H2S may serve as a neuroprotectant to treat TBI-induced brain injury via anti-apoptosis and suppression of excessive activation of autophagy therefore has potential clinical therapeutic value for treatment of TBI.
This field is still in its infancy and much will be learnt in the near future about the central roles play by H2S in health and disease

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