5-Aug-2020: Equipment-free, a simple paper-strip based naked-eye fluoride ion detection and quantification kit in drinking water to evade Fluorosis-based disorders

Fluorosis is a crippling disease resulting from deposition of fluorides in the hard and soft tissues of body due to excess intake of fluoride through drinking water/food products/industrial pollutants over a long period. It results in dental fluorosis, skeletal fluorosis, and non-skeletal fluorosis. Easy detection of fluorides in water can help preventing the public health hazards.

Scientists from the Institute of Nano Science and Technology (INST), an autonomous institute of the Department of Science and Technology, Government of India, have developed an equipment-free fluoride ion detection and quantification in drinking water with the naked-eye. It can be operated by non-experts for household use to evade Fluorosis-based disorders.

The technology developed by Dr. Jayamurugan Govindasamy and his team involves a push-pull chromophore based on 2,3-disubstituted 1,1,4,4-tetracyano-1,3-butadienes (TCBDs) that changes color upon exposure to fluoride ion. The identified chromophore (C3-phenyl, C2-urea functionalized TCBD) is the result of a systematic study seeded by the Early Career Research (ECR) Award and further supported by the Ramanujan Fellowship grant of DST received by Dr. Govindasamy. The results were recently published in the Journal of Organic Chemistry. The researchers designed urea as an unusual donating moiety instead of traditional donor moieties, such as amines, to obtain better optoelectronic properties. The charge-transfer (CT) property that arises through-bond in aniline donor is usually quenched due to photoinduced electron transfer (PET) mechanism. Whereas upon introducing urea as an electron donor, the CT exhibited both spaces as well as through bond due to “Field-effect”. Thus partial overcoming of PET process, which led to white light emission.

Later, they extended its applicability in sensing of biologically relevant fluoride, as it is well known that fluoride can bind with urea via H-bonding interaction. Thus the combination of the push-pull chromophore with urea turned out to be an ideal system for the same. The INST scientists have optimized the synthesis of this chromophore in the laboratory scale

Furthermore, the design and synthesis can be slightly modulated to increase the sensitivity from 3 ppm to less than 1 ppm. Currently, the INST team is working in this direction. The major cost involves only the synthesis of the chromophore, making it affordable and accessible.

Currently available, commercial kits for F– detection need analytical methods, mainly spectrometers (mobile or static). Some colorimetric detection kits are available, but they have some handling issues like work only with pH<1 (use of HCl), etc. The kit developed by the INST scientists’ scores above these in its ease of usage.

Although a vast number of reports are available for chromogenic and chromo-fluorogenic receptors in solution, only a limited number of reports which studied solid-phase detection. However, all those receptors suffer some drawbacks such as they generally exhibit color change only in organic medium and inorganic fluoride source, competing for affinity towards other anions such as acetate and phosphate, with a relatively high minimum detection limit of 10–30 ppm, work only with concentrated HCl, use of metals, delayed response, etc. while some works only with UV-lamp and chemically treated paper.

The non-planar push-pull chromophores sense fluoride ion with the naked eye in both solutions- as well as solid-phases.

The invention has been protected by filing the patent (202011028595). This work was supported by DST-SERB through the Early Career Research Award and Ramanujan Fellowship to Dr. Jayamurugan Govindasamy.

Several companies sell solution-based photometric as well as colorimetric sensor kit, including few Indian companies. However, there is no single product based on low-cost paper-strip available to bring down the cost of the kit as well as easy handling by layman.

Currently, one German company sells a paper-strip test kit for detection of HF with sensitivity of upto 20 ppm that too works only with hydrochloric acid (pH<1). This kit developed by INST can be used by non-expert, with high sensitivity up to 3 ppm in aqueous/DMSO 1:1 condition and with only DMSO upto 1 ppm and free of dangerous chemicals and equipments.

2-Aug-2020: INST scientists develop simple economical nonsurgical prevention of cataract

Cataract a major form of blindness that occurs when the structure of crystallin proteins that make up the lens in our eyes deteriorates, causing damaged or disorganized proteins to aggregate and form a milky blue or brown layer, which ultimately affects lens transparency. Thus, prevention of the formation of these aggregates as well as their destruction in the early stage of disease progression is a major treatment strategy for cataracts, and materials that can carry out this task could make cataract prevention affordable and accessible.

A team of scientists from the Institute of Nano Science & Technology (INST) an autonomous institute under the Department of Science & Technology, Government of India has developed nanorods from the nonsteroidal anti-inflammatory drug (NSAID) Aspirin, a popular medication used to reduce pain, fever, or inflammation and found it to be an effective non–invasive small molecule-based nanotherapeutics against cataract.

Their research published in the Journal of Materials Chemistry B could help prevent cataracts in an economical and less complicated way. They have used the anti-aggregation ability of self-build aspirin nanorods as an effective non –invasive small molecule-based nanotherapeutics against cataract. Aspirin nanorods prevent the aggregation of crystallin protein and various peptides derived from its fragmentation, which play a crucial role in cataract formation. They prevent the protein/peptide aggregation through biomolecular interactions, which convert beta-turn like the structure of the crystallin peptides, responsible for amyloid formation into coils and helices, those fail to aggregate. These were found to prevent cataract formation by inhibiting aggregation of crystallin, and crystallin derived peptide aggregates.  As with aging and under various conditions, the lens protein crystallin aggregates to form opaque structures in the eye lens, which impairs vision and cause cataract.

The targeted disaggregation of the accumulated alpha-crystallin protein and crystallin derived peptide aggregates in aged and cataractous human lenses are considered as a viable therapeutic strategy for the prevention of cataract formation. The aspirin nanorods are produced using the process of molecular self-assembly, which is a low cost and high –yield technique to generate the aspirin nanorods as compared to the high cost and laborious physical methods generally used for the synthesis of nanoparticles.

Computational studies based on molecular dynamics (MD) simulations were performed to investigate the molecular mechanism of aspirin’s anti-aggregation behaviour and the nature of protein (peptide)-inhibitor interactions between the synthetic peptides and aspirin. It was observed that the peptide-aspirin (inhibitor) interactions eventually transformed peptides secondary structures from beta-turns, those are responsible for the amyloids formation, into various coils and helixes, preventing its aggregation. These simulations revealed the secret behind aspirin’s ability to act as a potential inhibitor towards amyloid-like fibril formation by the model cataract peptides.

Many natural compounds have already been reported as potential aggregation inhibitors for crystallin aggregation, but the utility of nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin in this direction will open a new paradigm. In addition, aspirin nanorods due to their nano-size will enhance bioavailability, improve drug loading, lower toxicity, etc. Hence, the delivery of the aspirin nanorods as eye drops is going to serve as an effective and viable option to treat cataract non-invasively.

This easy to use and low-cost alternative nonsurgical treatment method will benefit patients in developing countries who cannot access expensive cataract treatments and surgeries.

29-Jul-2020: Dr. Harsh Vardhan releases book on Standard Treatment Guidelines for of Substance Use Disorders (SUD) and Behavioral Addictions

Dr. Harsh Vardhan, Union Minister of Health and Family Welfare released the e-book titled “Standard Treatment Guidelines for the Management of Substance Use Disorders and Behavioural Addictions” that aims to tackle substance abuse and behavioral addiction in the country, here today, through video conference, in the presence of Sh. Ashwini Kumar Choubey, MoS (HFW).

Speaking on Substance Use Disorder as a growing public health problem, especially among youth and adolescents, Sh. Ashwini K. Choubey said, “such problems will become more rampant as society adopts modern lifestyle. The Behavioural change also manifests in increased rate of suicides which we have seen during the COVID pandemic.” He commended the Drug Deaddiction Program (DDAP) under the Health Ministry and other stakeholders for implementing such initiatives across throughout the country.

Dr. Harsh Vardhan spoke on “the harmful association of Substance Use with non-communicable disorders (NCDs) like cardiovascular, cancer, road traffic injury, as well as mental health is well established.” He also expressed his satisfaction that “behavioural addictions like gambling, shopping, cyber-relational and cyber-sexual addictions including over-involvement in online relationship and pornography and addiction to online games has been included in the standard treatment guidelines.”

On the importance of addressing challenges to addiction in the times of COVID-19, Dr Harsh Vardhan cautioned that the World Drug Report 2020 “suggests that COVID-19 can have other fallouts just like earlier economic crises have caused – users seeking out cheaper synthetic substances; a shift to more injecting; economic downturn causing the poor and disadvantaged to turn to drug use and suffer its consequences.” He also elaborated on the “emerging evidence that smoking increases risk for COVID-19 as well as worsens the outcome in people who get infected with the virus. Alcohol intoxication can also increase the risk and the other effects including a reduction of immunity can increase the risk.” Similar effects can be anticipated with other drugs as well, he added.

Recollecting his experience in implementing WHO’s essential drug policy as the Health Minister of NCT of Delhi, he underscored the relevance of having a set of standard guidelines to help health professionals in preventing as well as minimising the harm from drug use. He said that the “Standard Treatment Guideline (STG) developed by the DDAP outlines a robust recommendation about the management of various Substance use Disorders or Addiction such that every general clinic can follow them.” He hoped “these Guidelines will help towards reducing the treatment gap for substance use disorders and help the country in its progress towards becoming healthier, happier and more prosperous.”

Impressed with the success of Government campaign to instill COVID appropriate behaviour in the masses such that every child is as aware of the norms as the expert recommending them, he pressed the need for a mass campaign to address the issue.  “This is a social issue not limited to the medical fraternity. Individuals in public life and religious organizations should also be involved in raising awareness. Awareness and cooperation between society and medical fraternity to fight the menace of addiction imminent for realisation of the Prime Minister's Vision of New India”

The National Mental Health Survey 1996 showed a treatment gap of 76-85% for substance use disorders mostly related to addiction to tobacco, alcohol, cannabis and opioids. The Standard Treatment Guidelines are developed by an Expert Group identified by the Tobacco Control and Drug Dependence and Treatment Programme (TC and DDAP). The group consists of psychiatrists working in the area of substance use prevention and treatment from National Institute of Mental Health and Neuro-Science  (NIMHANS), Bengaluru, AIIMS, New Delhi, Postgraduate Institute of Medical Education and Research  (PGIMER), Chandigarh, Vardhman Mahavir Medical College  (VMMC) and Safdarjung Hospital, Atal Bihari Vajpayee Institute of Medical Sciences (ABVIMS) and Dr. RML Hospital. The Guidelines are also available through the digital library of resources, available at: http://books.vknnimhans.in/books/jllx/#p=1.

This library has potential to be expanded in terms of regional, national and international resources that can be used for substance use treatment programmes in the country. The appendix contains an E-repository of resources in the area. Digital training of doctors through this book aims to reach the under-served populations through doctors and health professionals working in remote and poorly resourced settings.

Ms. Preeti Sudan, Health Secretary, Shri Rajesh Bhushan, OSD (HFW) and senior officials of the Ministry were also present. Dr. Rakesh Chadda, HoD, NDDTC, AIIMS, New Delhi, Dr. BN Gangadhar, Director, NIMHANS, Bengaluru and contributors to the book joined the programme through virtual platforms.