Asthma can be triggered by cigarette smoke

By Manjula FERNANDO

A beautiful girl, about three years of age was sleeping on the shoulder of an elderly woman. The fair complexioned girl with long strands of curly black hair on her face caught my eye, although she looked frail and unusually pale.

Using inhaler with spacer mask

A paediatrician at the Lady Ridgeway Children's Hospital examined the child. Soon after she was sent away to a treatment ward, Consultant Paediatrician Dr. Deepal Perera spoke to the Sunday Observer. But not before speaking to the grandmother of the child and said' "ask your husband to stop smoking immediately".

Beginning the conversation he said smoking has become a curse for our younger generation. The little girl was there to get treatment for asthma. For those who do not know the situation with asthma, it is a terrible sickness. How an asthmatic suffers for breath is sickening to watch, if not for modern day wonders of medication. The girl has got asthma because her grandfather is a chain smoker.

Dr. Perera began to explain the situation with asthma and wheezing among children and the position in Sri Lanka.

Infants up to six months can have noisy breathing which is a normal condition. A high pitched sound (a strido) can be heard when the child breathes in. This is due to a condition called congenital laryngeal stridor, caused due to a birth defect in the voice box.

In most conditions this will settle within the first six to 18 months but sometimes in a persistent condition the child may have to be referred to a doctor for medication. This is due to asthma or wheezing triggered by any allergic condition.

What is an asthma attack?

The mucous membranes in the small branches of the airways (bronchi) swell and the circular muscles contract ('spasm' or bronchospasm).

More mucus is produced in the already restricted airways, which makes breathing a struggle. This usually produces a wheezing sound, when breathing out.

How to identify if a child is wheezing:

Shortness of breath,

Respiratory breaths can be higher than his or her age, for a child under five years the respiratory is 50 breaths per minute.A dry cough without a cold, especially nocturnal coughing (night cough), aggravated when he is in a lying down position.

The child between three to 15 years may have bouts of a cough that makes him wake up in the middle of the night.

Dislike for physical activity

Persistent and prolonged cold

In severe cases -

The skin may change colour to white or blue (especially on the lips)

Frothing

Filariasis and TB

But the child could also be having nocturnal coughing due to filariasis as well. This and the possibility of Tubeculosis (TB) has to be ruled out if the child is suffering from persistent cough or night coughs before treatment for wheezing can be given.

According to doctors, a child could contract TB from an adult.

Transmission from another child has not been established.

Thus the family should first ascertain if a member of the family is having TB but has gone undetected before checking out the possibility of contraction from daycare, school, etc.

The child could also show suprasternal recession (a hollow appearing below the neck while breathing in) or intercostal recession (inward movement between the ribs while breathing in) when he is straining to breathe while having an attack of wheezing.

A sleeping child may change his position to a 'bent inward sitting position' to ease breathing.

There are no specialist paediatricians for asthma in Sri Lanka at the moment. The child has to be referred to a general paediatrician. In the future there will be specialised respiratory paediatricians.

What causes asthma in children? In young pre-school children, wheezing is usually brought on by a viral infection causing a cold, ear or throat infection.

Some people call this 'viral-induced wheeze' or 'wheezy bronchitis', whilst others call it asthma.

Most children will grow out of it, as they get to school age.

In older children, viruses are still the commonest cause of wheezing.

But other allergens may also cause an asthma attack like those listed below:

pollen, eg grass or birch

animal hair or fur

food, eg milk or eggs

house dust mites

fungus.

The most common factor for wheezing in Sri Lanka is dust. However, wheezing due to allergies caused by pollen can be ruled out since there is no pollen season here.

Dr. Perera says if a young child is asthmatic or shows allergic reactions to water, sand or pets, the child should not be immediately taken away from these allergens as water and sand play and playing with pets are closely related to his mental growth and may have a greater negative effect than the health risk.

What makes the condition worse

Exposure to situation for which they are allergic

Cigarette/pipe smoke

Colds

Pollution and dust

Exertion or exercise

If the child is allergic to dust, the mattress and pillows should be covered in polythene. Curtains and mosquito nets should be washed every two weeks. Thick blankets and clothes should not be used.

Padded, non-washable chairs too are not recommended.

Execising however, should be encouraged while relieving the condition with medication

A significant number of children brought to Lady Ridgeway Hospital with wheezing, have developed the condition due to cigarette smoke. In most of these instances the child has a grandfather who smokes at home.

Even if the smoker does it outside, he brings the smoke into the house in his clothes and this is enough for a child to develop asthma.

Dr. Perera said this is a serious situation in Sri Lanka.

When is it the right time to see a doctor?

When you suspect the child is having asthma or if the medication (relievers) he is already using is not responding, the child should be taken to a doctor.

Emergency

If the child has difficulty in breathing and the condition seems to be getting worse. If the child's skin colour changes or if the (salbutamol) ventolin puffer has to be used every four hours, for a longer period the child has to be taken to a hospital immediately.

Medication

In an acute attack of asthma you need nebulisation with salbutamol and ipratropium. This can be done in a hospital. If it is a mild attack after one nebulisation, the child will be sent home.

In an acute attack the medication has to be combined with steroids.

Parents should not be afraid of the use of steroids. This will be prescribed for five days. Steroids control asthma for a longer period, while salbutamol is used for immediate relief.

Medicines for asthma can be separated in two main groups.

Relievers : These are quick-acting drugs that relax the muscles of the airways.

They relieve the symptoms of wheeze, cough and breathlessness and are the first-line treatment of an acute asthmatic attack.

eg. ventolin evohaler

Preventers : These act over a longer time and work by reducing the inflammation within the airways.Parents should never be afraid to use inhalers as they carry minimal side effects compared to orally taken medications.

For very young children who are unable to use the inhaler alone will be recommended the use of a spacer and a mask by the paediatrician.

Swallowing not required for bitterness to induce nausea

The mere taste of something extremely bitter - even if you don't swallow it at all - is enough to cause that dreaded feeling of nausea and to set your stomach churning, according to a new study reported in the April 12th issue of Current Biology, a Cell Press publication.

"This work shows that our body and our physiology anticipate the consequences of foods we might eat, even if those foods contain toxins or anti-nutrients," said Paul Breslin of the Monell Chemical Senses Centre and Rutgers University. Of course, it is well known that the promise of something tempting to eat can cause a physiological response. Think Pavlov and his salivating dog. It also seems intuitive that bitterness, a taste associated with most plant-derived toxins, might be linked to nausea. However, Breslin says, the evidence was lacking.

In the current study, Breslin and the study's first author, Catherine Peyrot des Gachons, asked 63 healthy (and brave) individuals to sample an intensely bitter but non-toxic solution. He says the flavour could be compared to a typical concoction of liquid cold and flu medication on the bitterness scale. Participants held the bitter solution in their mouths for 3 minutes before spitting it back out. The experience led most people to report feelings of nausea that were either mild to moderate or strong. A second bitter solution had the same effect on people, unlike sweet, salty, or umami tastes.

During the taste-testing sessions, the researchers also recorded the electrical activity in the stomach using electrodes. Certain irregular patterns of stomach muscle activity are a hallmark of nausea, Breslin explained.

Those results made it clear that the self-reported nausea wasn't all in the study participants' heads. The exposure to bitter solutions produced responses in the stomach that were comparable to those caused by extreme motion sickness, the researchers report."It was known that our body can anticipate the ingestion of nutrients and prepare for them," Breslin said. "It was not known if our bodies anticipated the ingestion of toxins or anti-nutrients and prepared for this. Here we show that our bodies punish us for holding strong toxins in the mouth and that our stomachs respond so as to trap them and likely vomit them back up if swallowed." The findings suggest that those already prone to nausea - including pregnant women and patients undergoing chemotherapy - should take particular care to avoid bitter tastes. "In some instances, extreme nausea is worse than extreme pain, and anything we can do to help manage this is important," Breslin said.

(Source: Elisabeth Lyons Cell Press)

Study illuminates the role of laminin in cancer formation

Laminin, long thought to be only a structural support protein in the microenvironment of breast and other epithelial tissue, is "famous" for its cross-like shape. However, laminin is far more than just a support player with a "pretty face." Two studies led by one of the world's foremost breast cancer scientists have shown how laminin plays a central role in the development of breast cancer, the second most leading cause of cancer death among women in the United States. In one study it was shown how laminin influences the genetic information inside a cell's nucleus. In the other study it was shown how destruction of laminin can play a detrimental role in the early stages of tumour development.

Mina Bissell holds the title of "Distinguished Scientist" with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab). She is famous for having discovered the critical role in breast cancer development played by the extracelluar matrix (ECM), the network of fibrous and globular proteins surrounding a breast cell. Her "dynamic reciprocity" theory holds that the fate of cells whether they stay healthy or become cancerous - hinges on the chemical signals exchanged between the ECM and a cell's nucleus. In these latest studies, Bissell and her collaborators focused on laminin and its connections with two other proteins - actin, a cytoplasmic protein that has been linked to nuclear activities; and MMP9, an enzyme that is secreted outside the cells and is known to break down ECM constituents.

Laminin and cell quiescence

"Quiescence" is the process by which a biological cell stops growing or dividing. This is the opposite of a cancerous state, in which cell growth and division is often unchecked. Signals from laminin-111, an ECM protein that helps the cell and its ECM stick together, have been linked to cell quiescence but the mechanism was unknown. Bissell and postdoctoral fellow, Virginia Spencer, in Berkeley Lab's Life Sciences Division, have now shown that the addition of laminin-111 leads to quiescence in breast epithelial cells through changes in nuclear actin.

"We found that high levels of laminin-111 depleted nuclear actin and this in turn induced cell quiescence," Bissell says. "Furthermore, this process can be prevented if a form of actin that can not exit the nucleus is introduced. Under these conditions the cells do not stop growing even in the presence of laminin."

In their study, Bissell and Spencer and their colleagues used a unique three-dimensional cell culture assay developed by Bissell's research group, and worked with mouse and human mammary epithelial cells.

Through the addition of laminin-111, they were able to decrease nuclear actin levels in the cultured cells, which reduced DNA synthesis and transcription. When nuclear actin levels were deliberately over-expressed, the effects were reversed and cells were prevented from becoming quiescent even in the presence of laminin-111.

Furthermore, the high levels of nuclear actin were concentrated in regions of the breast cells where there was little or no laminin-111.

Taken together, the results implicate laminin-111 as the regulator of nuclear actin and nuclear actin as a key mediator of epithelial cell quiescence.

"In collaboration with Ole Petersen's laboratory, we had found previously that the ECM surrounding tissues from breast cancers has a dramatic reduction in laminin-111 in comparison to the ECM surrounding a normal breast cell, which is rich in laminin-111," Bissell says. "However, just giving laminin back to cancer cells was not enough to make them normal so other factors are clearly also involved and one such factor we now know is how laminin-111 and nuclear actin talk to each other!"

Says Spencer, "Ours is the first study to actually identify laminin-111 as the physiological regulator of nuclear actin and to implicate the loss of nuclear actin as a key step in reaching quiescence and homeostasis in the mammary gland in vivo and in culture."

Spencer believes that the interaction between laminin-111 and nuclear actin could provide a new target for diagnostic therapeutic efforts, but this will require further study.

"While it remains to be determined whether dysregulation of the levels or organization of nuclear actin is responsible for the inability of malignant cells to respond to growth-inhibitory signals from laminin-111, our preliminary results point in this direction," she says. "In addition, the findings that laminin-111 expression is lost in myoepithelial cells isolated from human tumours should place the interaction of laminin-111 and breast tumour cells at the forefront of future investigations."A paper detailing the results of this study appears in the Journal of Cell Science. The paper is titled "Depletion of nuclear actin is a key mediator of quiescence in epithelial cells." Co-authoring the paper with Bissell and Spencer were Sylvain Costes, Jamie Inman, Ren Xu, James Chen and Michael Hendzel.

Laminin, MMP9 and tumour growth

In the second study, which was related to the role of laminin-111 in cell quiescence, Bissell and another group of collaborators examined laminin-111 in the context of matrix metalloproteinase-9 (MMP9), a zinc-dependent enzyme that plays a huge role in tissue function by virtue of its ability to cleave or degrade many of the ECM constituent proteins, including laminin-111.

"Organization into polarized three-dimensional tissue structures defines whether epithelial cells are normal or malignant," Bissell says. "We have shown that when MMP9 degrades laminin-111 in the ECM, the tissue architecture of breast cells becomes lost and cell proliferation is initiated. This is the first demonstration of how the degradation of laminin-111 by MMP9 in a physiological context contributes to tumour progression."

A paper detailing the results of this study has appeared in the journal Genes and Development. The paper is titled "Raf-induced MMP9 Disrupts Tissue Architecture of Human Breast Cells in Three-Dimensional Culture and is Necessary for Tumour Growth in vivo." Co-authoring the paper with Bissell were Alain Beliveau, Joni Mott, Alvin Lo, Emily Chen, Antonius Koller, Paul Yaswen and John Muschler.

Using a model of human breast cancer where breast epithelial cells were grown in three-dimensional cultures of basement membrane, a thin layer of ECM material that envelops breast and other glandular tissue, Bissell and her co-authors found that not only did excessive MMP9 activity disrupt tissue architecture, but that silencing MMP9 restored tissue architecture and decreased the ability of human breast cancer cells to form tumours in mice.

"We found that in all conditions where tumour cells could be reverted to a normal phenotype in our 3D assays, a novel signalling loop through a pathway of Raf/MEK/ERK proteins was responsible for MMP9 activity in the breast tumour cells," says co-author Joni Mott, a researcher with Bissell's group in Berkeley Lab's Life Sciences Division. "Once MMP9 was activated, the proteinase targeted the destruction of laminin-111 within the basement membrane."

Laminin-111 in the basement membrane, Mott explains, allows mammary epithelial cells to establish a normal polarized structural unit called an "acinus," which is responsible for storing milk and making it available for babies when they suckle.

In their Genes and Development paper, Bissell, Mott and their co-authors reported that when the integrity of the tissue architecture was compromised by laminin proteolysis, the basement membrane no longer provided the appropriate signals to restrain epithelial cell proliferation. The result was a sustained signalling of the Raf/MEK/ERK pathway that leads to continued MMP9 production and further disruption of tissue architecture and loss of cell growth control.

"This work is particularly poignant because it provides potential new therapeutic targets for controlling breast cancer and revitalizes the possibility of targeting MMPs in cancer therapy," Bissell says. "New information on how MMP9 and other MMPs truly function may provide highly targeted and effective therapeutic strategies to control MMP activity in cancer, and may soon lead to the development of novel cancer treatments."Both studies were funded in part by grants from the U.S. Department of Energy's Office of Science, the National Cancer Institute, and the U.S. Department of Defence.

Source: Lynn Yarris DOE/Lawrence Berkeley National Laboratory.

Delhi superbug poses risk to antibiotic treatment worldwide

by Jeremy Laurance

An estimated 500,000 people in Delhi are carrying bacteria highly resistant to antibiotics acquired from drinking water, say researchers.

Tests on drains and public taps across the city found high levels of contamination with bacteria carrying the NDM 1 gene (New Delhi metallo-beta-lactamase) which confers resistance to almost all known antibiotics.

The discovery highlights the global threat from the spread of untreatable superbugs.

An estimated 25,000 people die each year in the European Union from antibiotic resistant bacterial infections.

The numbers affected beyond the EU are not known. Researchers from Cardiff University tested water samples from drains and public taps in Delhi.

They found 4 per cent of drinking water samples and 30 per cent of drain samples contaminated with the NDM 1 gene. Further tests showed the gene had spread to bacteria causing cholera and dysentery making them potentially untreatable.

Mark Toleman, an author of the study published in the Lancet Infectious Diseases, said: "Half a million people in New Delhi are carrying NDM 1 bacteria as normal gut flora.

"If we let it go, in the next two or three years we will see the loss of antibiotics in India.

We will rapidly get to the stage where those bacteria are untreatable."

Separate research showed that more than 80 per cent of travellers returning from India to Europe carried the NDM gene in their gut. NDM confers resistance to the most powerful antibiotics carbapanems.

Bacteria testing positive for NDM 1 genes had been isolated from 70 patients in the UK, according to the Health Protection Agency, but there had been no cases of onward transmission.

Dr Toleman said the situation in India and the rest of south-east Asia, which was the largest reservoir of NDM containing bacteria, posed a threat to the world, and international efforts were needed to improve sanitation.

He said the Indian government had expressed concern, but its hidden attitude was one of denial. Researchers investigating contamination of the water supply had been harassed.

At a briefing organised by the World Health Organisation, scientists warned that reckless use of antibiotics was in danger of returning the world to a pre-antibiotic era where infections did not respond to treatment.

David Heymann, chairman of the UK Health Protection Agency said that within two years of Penicillin being discovered, 11 per cent of strains of staphylococcus aureus were resistant and by the late 1990s over 90 per cent of hospital strains were resistant.

Courtesy: The Independent