Langerhan's cells histiocytosis: Phase IV trials begin in India

2009
By Syed Akbar
Hyderabad: Hundreds of medical experts and researchers from across the country will collaborate with their counterparts in the USA to finalise a safe drug for a strange and rare disease that afflicts mainly children below two years of age.

Called the Langerhan's cells histiocytosis or simply LCH, the disease
mimics cancer but it is not carcinogenic in nature. It affects several
parts of the body and is a complicated disease, which for decades was
thought to be a form of cancer.

The Histiocyte Society of the United States has sought the help of
medical colleges, hospitals and experts for a network to carryout the
LCH trial in the Indian sub-continent. The trials will begin later this
month. The reference centre will be Vienna, Austria. Drugs that have
been developed to fight this rare disease have already undergone three
phases and the participation of Indians in the fourth phase trials
assumes significance since there are several LCH patients in the sub-
continent.

According to Dr T Vasantha, who is coordinating the trials in the
country, histiocytosis is a very difficult disease to explain and
understand. The disease affects bones, pituitary gland, eyes, liver,
spleen, bone marrow and skin.

This is a randomised trial and randomisation takes place at Indian
Council of Medical Research. The All-India Institute of Medical
Sciences is coordinating the study. Treatment for this rare disease has
been approved and is being marketed. The present study is to evaluate
side effects that were not apparent in the phase III trial. Thousands of
people will be involved in the present phase.

"Medical colleges and hospitals will send samples to AIIMS which in
turn will forward them to the Histiocyte Society," Dr Vasantha said.

HIV-HCV coinfection highest in South India

2009
By Syed Akbar
Hyderabad, Feb 3: HIV patients from South India are two times more
prone to Hepatitis C virus coinfection than their counterparts living in
the North.

Researchers at the city-based Centre for Liver Research and
Diagnostics and the department of biotechnology, Jawaharlal Nehru
Technology University, found that the incidence of HIV and hepatitis C
virus coinfection is 3.02 per cent among HIV patients living down the
Vindhyas. The average coinfection rate for all-India is about 1.5 per
cent.

This in other words means South Indians are more susceptible to
coinfection of HIV and HCV as compared to North Indians. The study
was conducted among others by Dr CM Habibullah, Dr MN Khaja and
Dr M Chandra.

A greater proportion of HIV/HCV coinfected people may progress to
cirrhosis (serious liver scarring) and liver disease than those with HCV
alone. HIV-infected individuals have a high probability of getting
coinfected with HCV.

The team took the samples of 1487 confirmed HIV-positive patients
and tested them for anti-HCV antibodies. Of this, 1443 (97.04 per cent)
were negative and 45 (3.02 per cent) were coinfected. HIV-HCV
coinfection was predominant in the age group 41-50 years (51.1 per
cent).

"The results showed that HIV and HCV seroprevalence is higher in
South India, and the most prevalent genotype in coinfection was
genotype 1b," Dr Khaja told this correspondent.

"Prolonged survival of HIV-infected patients coinfected with HCV
may become an important clinical problem. HIV and HCV show some
common biological features like both are RNA viruses and both show a
large heterogenicity of their viral genomes producing various
genotypes," Dr Khaja said.

Globally, a total of 39.5 million are living with HIV, of whom 5.7
million are from India. Acquired immunodeficiency syndrome has
grown more rapidly than the scientific progress of understanding how
to control the main causative agent.

Globally, hepatitis C virus has infected more than 170 million people
and thus represents a viral pandemic seven times more widespread than
infection with the HIV.
It is estimated that in India about 1.8-2.5 per cent of the population is
presently infected by HCV and about 20 million people are already
having HCV infection.

"The objective is determine the prevalence of HCV antibodies in the
HIV-infected Indian population. This is aimed at providing the baseline
data on HIV/HCV coinfection and gaining better understanding of the
public health issues," he pointed out.

The male predominance was more with 61.5 per cent compared to
females by 38.4 per cent and the median age was 37 years, ranging
from 20 to 55 years. Of them 1183 (79.5 per cent) were heterosexual,
69 (4.64 per cent) were intravenous drug users (IVDs), 45 (3.02 per
cent) were blood transfusion recipients, 115 (7.73 per cent) were
haemophiliacs and 75 (5.04 per cent) were unnoticed.

Tuberculosis Breakthrough: New molecule developed to fight Mycobacterium

2009
By Syed Akbar
Hyderabad, Feb 2: Indian scientists have developed a novel compound that would hit the killer tuberculosis bacteria and cure the disease, which claims about 1000 people everyday in the country.

The novel compound has been successfully tested in laboratory and if it works on human beings, a single drug will be sufficient to deal with the menace of tuberculosis. At present, those suffering from TB are made to take a daily
dose of four drugs. The new development will help in fighting the disease through a single drug. This will save money on medication and prevent side-effects related to multi-drug therapy.

Scientists at the city-based Centre for Cellular and Molecular Biology and the Delhi-based National Institute of Immunology have jointly created the compound. Multi-drug therapy is administered in TB cases as different drugs target different metabolic pathways in Mycobacterium, the causative pathogen, killing it. But the new compound has multiple functions and hits the select metabolic pathways in the bacteria to destroy it.

CCMB scientist Dr Rajan Shankarnarayanan, one of the team members, told this correspondent that the compound stops tuberculosis by hitting four of
the bacterium's crucial metabolic pathways at the same time. "The compound weakens the pathogen before finally destroying it. We have demonstrated it in laboratory tests. However, it takes time before it becomes practical in human beings," he said.

According to Dr Rajan, if everything goes on well, a single drug will help tackle the disease. "A single drug that targets multiple pathways could save time and money by eliminating the need to take so many drugs over a period of say six to nine months," he added.

Mycobacterium tuberculosis, the organism that causes tuberculosis, contains a layer of complex lipids on its outer membrane. The CCMB-NII team found out how the bacterium builds up this complex layer that acts as drug resistant. Once they have solved the mystery, they developed a compound that would hit the metabolic pathways of the causative agent.

Although TB bacteria has been known for centuries, tuberculosis still accounts for more than two million deaths every year. The causative agent has a complex arsenal of virulence factors and has evolved elaborate strategies to escape host surveillance. The cell envelope of the bacteria is endowed with complex lipids, many of which play an important role in its pathogenesis.

"The complex lipids displayed by Mycobacterium tuberculosis are a big factor in its pathogenicity and virulence. Since this single molecule could potentially grind the assembly line to a halt at different stages of infection, this approach provides tremendous opportunity to develop unique antituberculosis drugs," he said.

Muslims in search of GenX religious leadership in Andhra Pradesh

By Syed Akbar
Hyderabad: The Muslim community in Andhra Pradesh is now in search of GenX religious leadership to guide it through the challenges being thrown in by the fast changing world.
The Muslim religious leaders in the State have let down the community on more than one occasion with their old ideas, most of them impracticable in this modern day society. The average age of top Muslim religious scholars is 60 years and some of the Moulanas cannot walk without support. And they have been at the helm of religious affairs for as long as two to three decades, literally blocking the growth of young leaders.
In the absence of second-rung leadership there are instances of madrasas and religious institutions suffering heavily following the death of the chief promoter. A few institutions have been closed down causing untold hardship to students.
"Some of the Ulema in the State had grown to such a stature that they had become institutions by themselves. And when they died the institutions they had nourished for decades also suffered slow death. This would have been avoided had there been a second-rung young leadership," observes Moulana Abdul Kareem who is in his early 20s.
With the old Ulema refusing to make way for the GenX, an attempt is being made by a group of Muslim social and religious activists to create what they call the "Third Muslim Force" in the State. They want to take on the old Muslim political leadership on one hand and the old religious leadership on the other, through the proposed TMF movement. A series of meetings have been planned and six of them have been completed.
"Be it politics or religion, we have been seeing the same old faces at least for the past 20 years. It's high time they stepped down and encourage young leaders to occupy high positions in religious institutions and madrasas. We have made a beginning with like-minded Muslim leaders in the State to create an alternative force to old Muslim politicians and old Muslim Ulema," says State IUML general secretary Abdul Sattar Mujahed.
Social activist Mubhashiruddin Khurram squarely blames the Ulema for the lack of second-rung religious leadership in the State. "Most of these Ulema send their children and grand-children to English medium schools and consequently they do not find anyone in their family to don the mantle after them. Moreover, they do not trust outsiders. This makes things complicated for them. They continue to run the show as long as they live and the moment they die the institutions suffer. This bad," he observes.
Jamiat-e-Ulema Hind State president Hafiz Peerzada Shabbir Ali advocates the system of "Majlis-e-Shura" (consultative committee) in all the religious institutions in the State to encourage a blend of old and young leadership in the community. He points out that eminent Muslim institutions in north India including the Nadwatul Ulema and Darul Uloom Deoband follow the tradition of Shura with 21 members. "Why not this practice be followed in Andhra Pradesh? We generally do not allow young leaders to occupy top positions because they easily become emotional. They do not think with heart. What we need is a blend of old and new leadership for a balanced direction to the community," Shabbir argues.
However, All-India Personal Law Board general secretary Abdul Rahim Qureshi does not agree that there's a generation gap in the Muslim religious leadership in the State. "You find many young Muslim scholars in madarasas. If some of them have turned old while serving the institutions, we cannot blame them," says he.
The notable Muslim organisations in Hyderabad with old guards at the helm of affairs include Tameer-e-Millat, Amarat-e-Millat-e-Islamia, Jamia Nizamia, Sunni Ulema Board and Jamaat-e-Islami Hind. There had been no change in the top leadership for many years.
Eminent institutions like An-Noor (Moulana Taqiuddin), Idare Islami (Moulana Akbar Qasmi) and Sabeelus Salam (Moulana Rizwanul Qasmi) fell in deep trouble after the demise of their founders. The change in leadership has not been smooth in the case of Sabeelus Salam with different claimants to its vast property.
"Yes, the generation gap is being felt by young and educated people in the community. Many of the old Ulema do not know what's happening in this new world. One has to take pains to explain to them terminology like AIDS, condoms or new methods in family planning while obtaining fatwas," says educationist B Moinuddin, recalling his experience with one of the old scholars.

Consanguineous marriages result in the birth of deaf children

By Syed Akbar
Hyderabad: Children born of close relation wedlock are known to suffer from a variety of genetic disorders and a fresh study by a team of city doctors and geneticists shows that they are highly prone to congenital deafness too.
A joint study by the Institute of Genetics and Hospital for Genetic Diseases and the ENT department of Osmania General Hospital reveals that children born out of consanguineous marriages are two times more susceptible to congenital deafness than ordinary children. The study was conducted in Government ENT Hospital and in various schools for the deaf in and around Hyderabad. The subjects ranged from neonates to children up to 14 years of age.
Dr PP Reddy of the Institute of Genetics told this correspondent that
among various causes for deafness, consanguinity is an established high risk etiological factor.
"The results showed that 41.73 per cent of the cases were the products of consanguineous matings and 58.27 per cent were born to non-consanguineous parents. Further analysis revealed a high rate of consanguinity (44.53 per cent) in children with non syndromic deafness. The percentage of consanguineous marriages in Andhra Pradesh is 22.36 but the rate of deafness in children born out of such wedlock is 41.73 per cent," he pointed out.
He said hearing impairment had debilitating effects on children as it could retard individual's language acquisition skills and impair the overall development. It is rapidly increasing sensory deficit among human beings and accounts for one third of the entire disease burden in the world.
The world-wide prevalence of profound, congenital deafness is 11 per 10,000
children, and is attributable to genetic causes in at least 50 per cent of the cases. The survey indicated that one out of every 1000 children born in India showed profound hearing loss.
Dr Reddy said the siblings of consanguineous marriages have a significantly higher incidence of autosomal recessive diseases including hearing impairment. Marriages within the family increase the risk of hearing impairment and other diseases.
"The development of cochlea and hair cells is dependent on a genetic pathway called Planar Cell Polarity pathway. This pathway is involved in the formation of the polarised structure of the auditory sensory organ and
regulates the embryonic development. Genetic aberrations caused due to consanguinity disturb the pathway leading to congenital hearing loss," he said.

Heart diseases in India prevalent 28,000 years before Indus Valley Civilisation

January 20, 2009
By Syed Akbar
Hyderabad, Jan 19: Indians have been dying of heart attacks long
before the Indus Valley Civilisation, 5000 years ago.

According to a new research study by the city-based Centre for Cellular
and Molecular Biology, heart diseases in India predate the Indus Valley
Civilisation or the Vedic period by about 28,000 years.

The history of sudden deaths due to heart attacks in Indian populations
traces back to 33,000 years, when people began inhabiting the Indian
sub-continent. Since then heart attacks leading to sudden death have
been a common genetic phenomenon passing on from generation to
generation, making Indians more susceptible to heart problems.

According to Dr Lalji Singh, director of the Centre for Cellular and
Molecular Biology, there was a sudden and unexplainable change
(mutation) in the ancestral populations in India 33,000 years ago and
this is proving to be the "worst luck in the world". The gene in question
provides a protein to bind together the heart muscles. When it becomes
defective, it fails to bind the heart muscles making the heart to work
harder to pump blood. And at one stage in life, heart attack lead to
sudden deaths.

However, indigenous populations in the Andamans and in North-
Eastern States are free of this genetic mutation and hence not
susceptible to cardiac problems from which other Indians suffer.
"The indigenous populations of Andaman and Nicobar inhabited the
islands about 60,000 years ago and since they were isolated, they
escaped from the genetic mutation that occurred in those who came to
the mainland India 30,000 years later," Dr Kumaraswamy Thangaraj,
one of the team members which conducted the study on cardiac
diseases among Indians.

The wayward gene has persisted in the population for generations
because its effects usually develop only after people have had their
children.

According to the CCMB scientists, the lifetime risk of developing heart
failure is roughly one in five for a person aged 40 years. Now that the
defect has been identified, there is a new glimmer of hope. It could be
detected very early during pregnancy. If parents choose, a foetus
having two copies FO the defective gene (homozygous or both from
father and mother) could be aborted after genetic counselling. Carriers
of the defect could be identified at a young age by genetic screening
and advised to adopt a healthier lifestyle.

"Perhaps eventually new drugs could be developed to enhance the
degradation of the abnormal protein and postpone the onset of
symptoms. Cardiac stem cell transplant might be used very effectively
to expand the life span of the individuals who carry the deletion. There
is a market of 60 million people waiting for such therapy," they told
reporters here on Monday.

Two sets of genes are inherited, one from father and one from mother.
If both the sets of genes are defective, children die even before they
celebrate their fifth birthday. If one set is defective, the onset of heart
problems begin after 45 years of age.