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Monday, February 23, 2015

Effect of Treatment with Hypoglycemic agents (Anti-Diabetics) on Weight of Patient

It is utmost importent on the part of the treating physician to know, which drugs have the side effect on the weight of a patient; this is particularly true for diabetics.
In a study with median of 3 months the researchers observed the following in case of Hypoglycemic agents (Anti-Diabetics).
Classes of hypoglycemic drugs associated with the most weight gaininclude sulfonylureas and glitazones. The most obesogenic istolbutamide at a 2.8-kg gain, followed by pioglitazone at 2.6 kg, glyburide at 2.6 kg, glipizide at 2.2 kg, and glimepiride at 2.1 kg.
The most weight-neutral DPP4 inhibitors are sitagliptin at0.55 kg and nateglinide at 0.3 kg.
Metformin is leptogenic, with an associated reduction in weight of1.1 kg. Glucagon-like peptide-1 (GLP-1) agonists also may causeweight loss, with liraglutide leading the way at−1.7 kg and exenatide at −1.2 kg.
These have to be kept in view, while prescribing medicines for Type II diabetes.

Saturday, January 10, 2015

Role of 20 Minute Whole Blood Clotting Test (WBCT20) in Snake Bite

There may not be envenomation in each case of snake bite. Amount of venom injected to the body depend upon several factors. The symptoms and signs of envenomation may be as follows:

Symptoms & Signs

Sometimes, it becomes difficult on the part of the clinician to effectively distinguish between a poisonous snake bite from a non-poisonous snake bite in the early hours; whether to start treatment with Anti-Snake Venin (ASV) or not. 

To read about snake bite, go here.

Abnormality is blood coagulation is a distinguished feature of viper envenomation, though it may also be seen to some extent in other poisonous snake bites.

(In West Papua and the Maluku Islands, envenoming by Australasian elapids can cause incoagulable blood)

If, laboratory service is not available for better tests like Prothrombin Time (PT) and INR (International Normalised Ratio) to determine the abnormality in coagulation, an useful and informative bedside test requiring very little skill and only one piece of apparatus – a new, clean, dry, glass vessel (tube or bottle) may be helpful.

That is 20-minute whole blood clotting test (WBCT20)can be performed as described below:
  • Place 2 mls of freshly sampled venous blood in a small, new or heat cleaned,dry, glass vessel.

  • Leave undisturbed for 20 minutes at ambient temperature.
  • Tip the vessel once after 20 minutes.

            If, after 20 minutes:

  • The blood is still liquid (unclotted) and runs out, the patient has hypofibrinogenaemia (“incoagulable blood”) as a result of venom-induced consumption coagulopathy.
      (In the South-East Asia region, incoagulable blood is diagnostic of a viper bite and rules out an elapid bite)

Note: If the vessel used for the test is not made of ordinary glass, or if it has been cleaned with detergent, its wall may not stimulate clotting of the blood sample (surface activation of factor XI – Hageman factor) and test will be invalid.

If there is any doubt, repeat the test in duplicate, including a “control” (blood from a healthy person such as a relative)

Note of CautionThis test may not detect low level of envenomation, hence, cannot be relied upon fully to start the Anti-Snake Venin therapy; may result in delayed decision. 


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.
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