A team of Harvard scientists has taken the first step to solve mystery about why HIV patients are more susceptible to TB infection.
According to USAID, 42 million people are HIV infected & almost one third of them are also TB infected. It is believed that HIV interferes with the cellular and molecular mechanisms used by the lungs to fight TB infection.
This mystery has been solved when scientists extracted immune cells called “alveolar macrophages” from the lungs of asymptomatic HIV +ve patients as well as healthy patients ” HIV –ve.” They observed a decrease in response towards TB bacterium in HIV +ve patients when compared to HIV –ve patients.
A further examination of lung specimens showed an increased level of a molecule called IL-10, which elevates the amount of a protein called “BCL-3″ in alveolar macrophages and this reduces their ability to ward off TB infection.
It seems that HIV increases severity of TB infection, where both represent two of the most significant health challenges in human history.
Source: Science Daily.
Image credits: The HIV replication cycle.
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Researchers at Massachusetts General Hospital (MGH) are investigating a new way to block replication of hepatitis C virus “HCV” by targeting not the virus itself, but the genes that the virus exploits during its life cycle.
HCV has a high rate of replication that it can replicate a trillion particles per day. Also, due to its high rate of mutation, it can escape our immune system.
HCV replicates mainly within hepatocytes in liver by binding to receptors on the surface of the liver “CD81″ and human scavenger receptor class B1 “SR-BI”. Then it utilizes the intracellular machinery necessary for its replication.
Transmission occurs by blood to blood contact, where it causes chronic liver infection in about 70-80% of patients & long term infections can cause liver failure or liver cancer.
HCV infection is usually treated with a six to eleven month regimen combining peginterferon and the antiviral drug ribavirin, but unfortunately, treatment is not successful in many patients and has serious side effects that some cannot tolerate.
Many drugs target viral enzymes, but due to the great ability of HCV to mutate, such approach lead to the emergence of resistant strains.
Recently, a new strategy has developed, which is to block human genes, which act as a cofactors for HCV infection. Using small interfering RNAs (siRNAs), researchers examined blocking of approximately 21,000 predicted messenger RNA transcripts in the human genome.
The siRNA scan found 96 genes that appear to have a role in viral replication, one gene codes for an enzyme called PI4KA, which is believed to be involved in the formation of membrane structures within the cell. Another group of genes contribute to formation of the coat.
So, by blocking these genes, HCV replication is stopped. At this time, these tested agents might not be suitable for therapeutic use.
Source & Image credits : Harvard Science.
Tags: blood contact
, Massachusetts General Hospital
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Streptococcus pneumoniae is a pathogen normally found in nasopharynx of about 5-10 % of healthy people. Despite its name, it can cause many other diseases as meningitis, septic meningitis, otitis media, & osteomyelitis.
S. pneumoniae main virulence factors are:
a) Polysaccharide capsule: that inhibits phagocytosis.
b) Pneumolysin: a protein that causes lysis of host cells & activate complement.
c) Hydrogen peroxide: causes damage to host cells.
d) Pili: contribute in colonization of upper respiratory tract and increase the formation of large amounts of TNF.
Researchers led by Jesús M. Sanz at the Miguel Hernandez University and Maarten Merkx at the Eindhoven University of Technology have now introduced a highly promising new approach for the development of drugs to treat pneumococci.
The cell wall of pneumococci contains special polymers, called teichoic acids that are rich in choline which act as a docking station for a number of special proteins that are involved in important processes as:
1) Cell wall division.
2) Release of bacterial toxins.
3) Adhesion to infected tissues.
If choline is added to a culture of pneumococci, the molecules occupy the choline binding sites of the CBPs so that the proteins can no longer bind to the cell walls of the pneumococci.
The bacteria continue to multiply but they can’t separate from each other, these results in long chains of linked cells. Also, the toxin released is stopped.
However, choline is not suitable to be used as a drug because an effective dose would be far too high.
The researchers thus developed the foundation for a new drug that binds CBP much more strongly than individual choline molecules. The drug imitates the choline architecture of the cell wall by presenting multiple choline groups. This will occupy multiple choline binding sites of the CBP.
Also, the required dosage of this CBP inhibitor lies within the range that is acceptable for pharmaceuticals.
Source: Science Daily.
Image credits: S.pneumoniae.
Image credits: S.pneumoniae.
, choline binding sites
, otitis media
, Streptococcus pneumoniae
, teichoic acids
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Researchers at Penn state discovered two new proteins which activate cells in the immune system & cause a rare form of blood cancer.
Helper T-cells can stimulate B lymphocytes to produce antibodies against the pathogen. Also, stimulate cytotoxic T-cell that kills infected cells.
Shortly after the elimination of pathogen, most of cytotoxic T-cells die while few of them remain to protect the body from re-infection with the same pathogen.
In some cases of autoimmune diseases these cells don’t die, but they expand & attack many tissues as bones to cause rheumatoid arthritis “RA” or bone marrow to cause leukemia.
Researchers at Penn state tried to find out conditions that cause abnormal expansion of these cells, they made an intricate computer modeling which follows up signals involved in either activation or death of these cells.
The researchers have found two proteins “IL-15 and PDGF” which are needed to cause activation & proliferation of T-cells. IL-15 causes activation, while PDGF stimulates their growth.
Another signaling protein called “NFκB” controlled by the two proteins which prevent the death of cancer cells whatever they are over expressed.All those proteins may become targets for drugs; when they blocked NFκB with drugs in cells from leukemia patients, an increase in mortality of abnormal T-cells has been observed.
So, the key is to find out what stimulates T-cells to survive & proliferate.
Source: Science Daily.
Image credits: Immune response.
Tags: cytotoxic T-cell
, intricate computer modeling
, Penn state
, rheumatoid arthritis
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Nothing is impossible..
Things, you think are absolutely harmful, may be highly beneficial if we use them in a new way.
Viruses can be used in the treatment of cancer, a field known as oncolytic virotherapy.
But can you imagine that they are safer & highly specific than other traditional chemotherapy???
You will get the key when you know that they destroy cancer cells with a high accuracy that scientists called them “magic bullet”.
Simply, the mechanism of most viruses is to infect our cells, then to use them as a factory to produce more & more viruses.
Viruses are highly specific, they replicate in cells having receptors for them. So, we need to change viruses to selectively bind to tumors.
In fact, a virus consists of a coat & genome.
So, we got two methods to generate tumor selectivity.
First: By making modification on viral coat in order to increase adhesion between coat & cancer cells “Transductional Targeting”.
Second: By altering viral genome, so it can only replicate in cancer cells “Non-Transductional targeting”.
However, many primary cancers were resistant to conventional virotherapy.
Researchers at McGill University and the affiliated Lady Davis Research Institute of the Jewish General Hospital, along with colleagues at the University of Ottawa and the Ottawa Health Research Institute (OHRI) have discovered that a family of compounds called histone deacetylase inhibitors “HDI” which convert oncolytic viruses into more potent weapon.
So, HDI can augment the ability of the virus to target & kill the cancer cells.
Many viruses can be used especially those with dsDNA
genomes “as adenovirus and herpes simplex virus” where they have a higher stability & less susceptible for mutations.
Researchers utilize Vesicular Stomatitis Virus “VSV” as it is not a human pathogen. So, most individuals don’t have antibodies against it & can be treated before they gain immunity.
Human trials have been already approved & the results of these experiments will determine if this viral bullet is really a “magic bullet”.
Image credits: Vesicular Stomatitis Virus
Tags: cancer cells
, histone deacetylase inhibitors
, magic bullet
, non-transductional targeting
, traditional chemotherapy
, transductional targeting
, tumor selectivity
, vesicular stomatitis virus
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“Did you brush your teeth today ??”
I think you will ask this question to yourself & your family daily.
When you know that bad oral hygiene will drive you to heart disease, many of us may change his opinion.
Simply, people who don’t brush their teeth regularly will start with inflammation of their gums “Gingivitis“.
If this situation continues, a chronic inflammation occurs “Periodontal Disease“ with a bleeding gum.
Bleeding gum is a great risk factor, as it provides an entry to the blood stream for 700 different types of bacteria.
Streptococcus gordonii and Streptococcus sanguinis are two common infecting agents.
After they reach the blood stream, they bind with blood platelets, this creates two problems:
First: If we use an oral antibiotic to kill oral bacteria thus preventing them from reaching the blood stream, by time bacteria become resistant.
Second: The binding of bacteria with platelets encases them & shields bacteria from our immune system till they reach the heart causing heart diseases.
So, if we prevent the binding between bacteria & platelets, this will help our immune system kill bacteria & protect our heart.
“We are currently in the process of identifying the exact site at which the bacteria stick to the platelets” said Professor Howard Jenkinson. “Once this is identified we will design a new drug to prevent this interaction.”
Source: Bristol University news.
Image credits: Periodontal Disease
Image credits: Professor Howard Jenkinson
Tags: bleeding gum
, Heart Attack
, Periodontal Disease
, Streptococcus gordonii
, Streptococcus sanguinis
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It is something like a dream, Marijuana, which is known in Egypt as “Hashish “, is used now as an antibiotic.
Marijuana is a herb planted in many countries as middle east eastern, Europe & Africa.
It is ingested by smoking, which quickly delivers active ingredients to the blood system. Marijuana has analgesic, anti-emetic, anti-inflammatory, sedative, anti-convulsive, and laxative actions.
Also, it is used in chemotherapy to relieve nausea & vomiting and for AIDS patients as stomachic.
Scientists tested five major active ingredients called cannabinoids on Different strains of MRSA “methicillin resistant Staphylococcus aureus“.
Both natural & synthetic cannabinoids show germ killing activity against MRSA.
These active ingredients exhibit antibacterial activity in a different way, meaning that they might be able to bypass bacterial resistance.
At least two cannabinoids “out of 5″ can be used safely without causing mood alteration.
MRSA like other Staphylococcus spread by contact, so people of close contact are of high danger.
Finally, researchers in the Journal of Natural Products call for the further study of antibacterial uses of marijuana as it is too difficult to find new antibacterials since unfortunately, bacteria became resistant to them.
Source : Web MD
, methicillin resistant staphylococcus aureus
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