BioBank Relevant Links

Biobanks in Developing Countries: Needs and Feasibility
S. K. Sgaier,P. Jha,P. Mony,A. Kurpad,V. Lakshmi,R. Kumar,N. K. Ganguly
Science 16 November 2007:
Vol. 318. no. 5853, pp. 1074 - 1075
DOI: 10.1126/science.1149157

Futuristic biobanks
Neelam Pereira
CURRENT SCIENCE, VOL. 95, NO. 3, 10 AUGUST 2008

Human DNA Repository of Indian Population

This article talks about a private company LuVita trying to establish a biobank in India. No information about such a company is available on google. Check out Nowgen digest number 9 which talks about this and also 12 DNA repositories in India.

Neurological and Psychiatric BioBank

Dear All,
Recently I was speaking to Dr. Subbalakshmi, resident Neurologist at National Brain Research Centre, India and one of the topics of discussion was establishing a National Biobank specifically for Neurological and Psychiatric diseases.
Since 2007, ICMR is contemplating on establishing a biobank using DBS (dried blood samples) but concentrating on women, infectious diseases, cancer. It is carrying out feasibility surveys and the cost would be $10 per son thats nearly 500 rupees per person. SNP analysis is a possible and attainable goal of DBS collection.

However, we know that many genetic disorders exist in India and have the potential to give unique understanding of normal physiology of human being. Gene hunting in India is slowly catching up. In the neuroscience field, recent work by IISc and NIMHANS scientists, JNCASR and NIMHANS researchers has been a matter of joy. There is however a dire need for establishing a DNA collection facility for many of Neurological diseases and psychitric diseases. Consanguinous marriages in India is unfortunately still a reality, but rather than cursing it we can collect samples from such patients and establish a biobank.

India, being home of 100 crore+ people has not yet established a affordable and accessible genetic testing centre nationwide and people need to depend on private establishments totally. If health is the government concern, then it should come forward to deliver superior quality genetic testing. If we keep on thinking, genetic testing is a luxury compared to providing sanitation, drinking water and food, then we would still be 20 years behind all other nations including Mexico.

The point is it is possible to give genetic testing facility to common people at the same time accumulating biological samples for superior research, which can be done HERE in India. It has to be regional, probably state wise and a National centre to co-ordinate the regional ones. Many of the neurodegenerative cases, neurodevelopmental disorder cases are sent home with infused despair from esteemed neurological instituetes because treating neurologist would find no use in making their money go waste. They are right on their ethical stand point, but how long we keep this attitute. If India needs to be best in research we need to have that attitute, attitute with eagerness to learn, to establish the cause to the core, to find something new.

Also I feel, if we have a neurological and psychiatric diseases bank, we can help our own home grown researchers to gene hunt, to find out the cause and to get connected with the disease. How many basic scientists in India have seen even common diseases like Alzheimers, Parkinsons? Hardly countable number..but they still talk a lot about that disease, mainly because they have read about such diseases all through western media. WE in India have such diseases, people suffer and we do have world class physicians, scientists in biological field who work on them. We need not look at west all the time to connect ourselves with research. By giving, INDIAN biological samples it can be hoped that they connect well the disease they plan to study.

Biobank is not a new concept. Biobanks exist in USA, UK, Sweden, Finland, Hungary, Mexico and other countries. There are disease specific biobanks too, like Alzheimers, Psoriasis. Neurological and psychitric disease biobank exists in Hungary.

So, when are having it? I hope Dr. Ganguly, Dr. Tandon are listening to me!!!

Chandipura Virus-New Insights

This virus was discovered by NIV, Pune in 1965 in two adults suffering from febrile illness in Napur area of Maharashtra. It was isolated from sandflies around Aurangabad in 1970 (Dhanda V et al, IJMR,1970). Isolation have also been reported from Madhya Pradesh, Nigeria. In 2003, there was an encephalitis epidemic in Andhrapradhesh, Maharashtra just at monsoon onset and 183/329 children died in Andhrapradesh only. Patients complained abdominal pain had vomiting, acute enphalitis/encephalopathy features leading to death with in 48 hours of hospitalization. Neurological sequel in recovered cases is a rare occurrence which is a sigh of relief.

NIV which was established in 1952 under auspices of ICMR and Rockefellar Foundation has played a pivotal role in understanding this disease.

This virus belongs to Rabies virus family (Rhabdoviridae) and as shown in picture (taken from NIV, CHP virus poster) has bullet shape and lower stained canal!

Tripathy et al (Scand J Infect Dis. 2005;37(8):590-3)reported significant change in INF-Gamma, IL-2 compared to controls, whereas IL-6 and TNF-Alpha were higher in patients with >2 days of illness compared to controls.

Here authors show that there is blood brain barrier breach early in infection as measured by evans blue dye exclusion test. Young mice are susceptible to infection IV, IP and intracerebral mode where as adults are susceptible only via intracerebral route. Raise in proinflammatory cytokines like TNF-alpha, INF-gamma, IL2, IL6 with 24 hours of infection can aid leak in BBB. Authors also saw that IgM antibody for virus appears as early as 72 hours post infection which seems to decrease blood viral load but cant decrease CNS load. CD4+, CD8+ and CD19+ cells were also less in infected mice and antigen specific suppression of T cell proliferation was witnessed at 72 hours. Authors also report that passive immunization was able to prevent infection before viral infection and not at 24 hours post infection.

This paper is a significant step in understanding the etiopathogenesis of this viral infection.

Immune response during acute Chandipura viral infection in experimentally infected susceptible mice
Virol J. 2008; 5: 121. Published online 2008 October 20(click here to read the paper)

Anukumar Balakrishnan(1) and Akhilash Chandra Mishra(2)
1 Chandipura virus group
2 Director, National Institute of Virology, 20-A, Dr. Ambedkar Road, Post Box-11, Pune-411001, Maharashtra, India

Illegal Settlements in Brain

Neeraj Jain et al report large scale reorganization of somatosensory cortex in macaque monkey brain post partial or complete dorsal hemiresection of the cervical spinal cord. This work however was not done in India but at Vanderbilt university, USA where he did his postdoctoral work. He continues to map brain using similar methods at NBRC(His NBRC webpage).

Adult brains undergo large-scale plastic changes after peripheral and central injuries. Although it has been shown that both the cortical and thalamic representations can reorganize, uncertainties exist regarding the extent, nature, and time course of changes at each level. We have determined how cortical representations in the somatosensory area 3b and the ventroposterior (VP) nucleus of thalamus are affected by long standing unilateral dorsal column lesions at cervical levels in macaque monkeys. In monkeys with recovery periods of 22–23 months, the intact face inputs expanded into the deafferented hand region of area 3b after complete or partial lesions of the dorsal columns. The expansion of the face region could extend all the way medially into the leg and foot representations. In the same monkeys, similar expansions of the face representation take place in the VP nucleus of the thalamus, indicating that both these processing levels undergo similar reorganizations. The receptive fields of the expanded representations were similar in somatosensory cortex and thalamus. In two monkeys, we determined the extent of the brain reorganization immediately after dorsal column lesions. In these monkeys, the deafferented regions of area 3b and the VP nucleus became unresponsive to the peripheral touch immediately after the lesion. No reorganization was seen in the cortex or the VP nucleus. A comparison of the extents of deafferentation across the monkeys shows that even if the dorsal column lesion is partial, preserving most of the hand representation, it is sufficient to induce an expansion of the face representation.

The Journal of Neuroscience, October 22, 2008, 28(43):11042-11060

This is not exactly Neuroscience but has implications in it

Nanoclusters of GPI-anchored proteins are formed by cortical actin-driven activity.
Cell. 2008 Dec 12;135(6):1085-9
Goswami D, Gowrishankar K, Bilgrami S, Ghosh S, Raghupathy R, Chadda R, Vishwakarma R, Rao M, Mayor S.
National Centre for Biological Sciences (TIFR), Bellary Road, Bangalore 560065, India.

Several cell-surface lipid-tethered proteins exhibit a concentration-independent, cholesterol-sensitive organization of nanoscale clusters and monomers. To understand the mechanism of formation of these clusters, we investigate the spatial distribution and steady-state dynamics of fluorescently tagged GPI-anchored protein nanoclusters using high-spatial and temporal resolution FRET microscopy. These studies reveal a nonrandom spatial distribution of nanoclusters, concentrated in optically resolvable domains. Monitoring the dynamics of recovery of fluorescence intensity and anisotropy, we find that nanoclusters are immobile, and the dynamics of interconversion between nanoclusters and monomers, over a range of temperatures, is spatially heterogeneous and non-Arrhenius, with a sharp crossover coinciding with a reduction in the activity of cortical actin. Cholesterol depletion perturbs cortical actin and the spatial scale and interconversion dynamics of nanoclusters. Direct perturbations of cortical actin activity also affect the construction, dynamics, and spatial organization of nanoclusters. These results suggest a unique mechanism of complexation of cell-surface molecules regulated by cortical actin activity

Aluminium and Alzheimers'!!!

Sandeep Tripathi et al from CDRI, Lucknow are publishing their research in Brain Research Journal. The topic is controversial "Aluminium and Alzheimers disease" related. Issue was upheld when aluminium was detected in neurofibrillary tangles (DP Perl et al, Science, 1980)and a study suggested a geographical correlation between aluminium and alzheimers in the journal Lancet (C N Martyn et al, Lancet 1989). And so the story goes on. Aluminium is used in water cleaning, utensils etc and hence a potential for a toxic metal to induce neurological changes exists.

According to authors, aluminium ingestion (100mg/Kg) caused reduction in body weight, brain weight more evident in aged male wistar rats. Treated aged rats had less relearning index in Y-maze test compared to untreated or even young treated ones!

Aged as well as young treated rats had less protein, more lipid, more conjugated dienes, more lipid peroxides and hydroperoxides, more lipofuscin compared to untreated age-matched controls. They also had significant less levels of catalase, superoxide dismutase, glutathion reduced as well as peroxidase along with increased levels of Iron, decreased Selenium and Copper.

n=12 in each group (Young control and treated=~6 months, Aged control and treated=~24 months). Its not not clear to me atlest whether they gave 100mg/kg AlCl3 mixed with 1% gum acacia for 90days to treated group.

Overall, this paper suggests that aluminium has age related effects of inducing oxidative stress and causes accumulation of lipofuscin in frontal cortex of wistar rats.

I just want to comment that aluminium concentration used does seem to be too high.
Reiko Matsuda et al ( Journal of the Food Hygienic Society of Japan(2001)) suggest daily dietary intake to be 1.8 to 8.4 mg..we dont know whats the scenario in India).

Ciba Foundation Symposium 169 - Aluminium in Biology and Medicine book excert is given below. Author is J L Greger

Aluminium in the food supply comes from natural sources including water, food additives, and contamination by aluminium utensils and containers. Most unprocessed foods, except for certain herbs and tea leaves, contain low (<5 µg Al/g) levels of aluminium. Thus most adults consume 1-10 mg aluminium daily from natural sources. Cooking in aluminium containers often results in statistically significant, but not practically important, increases in the aluminium content of foods. Intake of aluminium from food additives varies greatly (0 to 95 mg Al daily) among residents in North America, with the median intake for adults being about 24 mg daily. Generally, the intake of aluminium from foods is less than 1% of that consumed by individuals using aluminium-containing pharmaceuticals. Currently the real scientific question is not the amount of aluminium in foods but the availability of the aluminium in foods and the sensitivity of some population groups to aluminium. Several dietary factors, including citrate, may affect the absorption of aluminium. Aluminium contamination of soy-based formulae when fed to premature infants with impaired kidney function and aluminium contamination of components of parenteral solutions (i.e. albumin, calcium and phosphorus salts) are of concern.

This "metal ions" causing problems theory is gonna stay untill we pinpoint the exact cause of Alzheimers disease and produce a perfect model of it (apart from current so called Alzheimer models..are majorly just models of amyloidosis kind of disorders!!)

Long way to go in this but this atleast lets us know of ill effects of Aluminium.

Influence of age on aluminum induced lipid peroxidation and neurolipofuscin in frontal cortex of rat brain: A behavioral, biochemical and ultrastructural study

Brain Research, Article in Press,
doi:10.1016/j.brainres.2008.11.060

Sandeep Tripathi,Abbas Ali Mahdi, Akbar Nawab, Ramesh Chander,Mahdi Hasan,Mohammad Shakil Siddiqui,Farzana Mahdi,Kalyan Mitra and Virendra Kumar Bajpai

Department of Biochemistry, King George’s Medical University
Department of Anatomy, King George’s Medical University
Department of Biochemistry, Era’s Lucknow Medical College
Electron Microscopy Division, Central Drug Research Institute, Lucknow, India 226003

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Another study in the Brain Research Journal by Kumar V et al (PGIMER, Chandigarh) reports impairment in mitochondrial energy metabolism in wistar rats receving 10mg/kg body weight aluminium for 12 weeks. They also found decreased levels of SOD and Glutathion as well as increased ROS.

Intake is still high compared to human estimates (10mg/60Kg=0.16mg/Kg)

Impairment of mitochondrial energy metabolism in different regions of rat brain following chronic exposure to aluminium.

Kumar V, Bal A, Gill KD.
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India.

Brain Res. 2008 Sep 26;1232:94-103. Epub 2008 Jul 16

Epilepsy Prevalence: Kolkata

This epidemiological study puts out interesting findings. According to the study (door to door stratified random sampling). Prevalence of active epilepsy (< or = 19 years of age) is in the range of 0.58-0.83 % which is well below average epilepsy prevalence 1% (see Satishchandra et al). However febrile seizures prevalence was found to be 0.9-1.2%. 9.5% of febrile seizures developed epilepsy later on which is higher than western data. One third of cerebral palsy patients had epilepsy.

This paper re-emphasizes our need to concentrate on epilepsy, diagnosis and treatment strategies.

Indian J Pediatr. 2008 Dec 4. [Epub ahead of print]
Neurological disorders in children and adolescents - An epidemiological study
Banerjee TK, Hazra A, Biswas A, Ray J, Roy T, Raut DK, Chaudhuri A, Das SK.
National Neurosciences Centre, Kolkata, India