News Article | February 15, 2017
Professor Sujoy K. Guha is undeniably stylish. A short, slender man, he is among the select few who can pull off a pair of sneakers with formal shirts and trousers. At 76, he is deceptively brisk, guiding me around the Indian Institute of Technology (IIT) Kharagpur campus to show off his new projects: an artificial heart modeled on the 13-chamber heart of the cockroach; a road transport system to lower vehicular pollution. Guha is cheerful and poised with a birdlike quaver in his voice, not at all how I expected a man who has waited 37 years for his work to be introduced to the world. In 1979, Guha published a paper in the scientific journal Contraception laying out the idea for his original drug molecule Risug, a non-hormonal, reversible male contraceptive. His idea is simple: All particles carry an electric charge and can be defused by the opposing charge. Sperm are negatively charged and can be defused by the positive ions of the Risug drug polymer. This polymer is inserted with a single injection to the scrotum, which forms an indissoluble film inside the vas deferens—the duct connecting the testes to the penis. The drug formulation for this injection is styrene maleic acid anhydride with dimethyl sulfoxide (SMA+DMSO). A male contraceptive is an unusual thing. Almost the entire range of contraceptive methods available target the female body. The UK's National Health Service website sums up this state of affairs well: out of 16 choices listed for 'methods of contraception', 13 are female. The options for men are condoms (a method whose effect is very limited-term), vasectomy (whose effect is irreversible) and withdrawal. In October of 2016, there was news that the clinical trial of a hormonal male contraceptive, in development for several years, was being stopped on account of side-effects experienced by trial subjects. As of this moment, Risug is possibly the only long-term, reversible male contraceptive in development in the world. (And it's non-hormonal and cheap to boot.) Two years ago, Motherboard wondered why Risug wasn't on the market yet. The average time for a drug to go from idea to market is 10 to 15 years (presumably in the developed world). Now, half of Guha's life later, the word from the Indian Council of Medical Research is that Risug is finally on the cusp of approval. Testing has been completed on 282 subjects across ten hospitals, and the results are nothing short of miraculous—Risug has shown complete effectiveness with zero side effects. A 2011 report by the Ministry of Health and Family Welfare mentioned finding no side effects for the drug in the long-term (a period of nine to ten years), as well as full efficacy. When the 300th volunteer is tested, the Indian Council of Medical Research will formally submit the application for approval to the Central Drugs Standard Control Organization, which is similar to the American FDA. An original drug molecule devised by an Indian individual is a very rare thing. Only two Indians have been credited with such an accomplishment—Dr. U.N. Brahmachari introduced Urea Stibamine to treat Kala Zar, a deadly tropical diseases carried through sand flies; and Dr. Amiyo B. Kar for Centchroman, a nonsteroidal female contraceptive. Guha will be the third. "I have shortlisted two sites for production in Delhi. The knowhow is ready, we just have to scale up from my lab workshop. The sale of my flat is almost finalized," Guha told me. "I am not waiting for a company any longer. I am a scientist, not a marketing man." The professor has been at this juncture before. Fourteen years ago, the then Union Health minister, who oversees public health programs, had announced the imminent availability of Risug in the market, and the news was published in leading national dailies. Just before this, the Ministry of Health and Family Welfare had announced an extension of the clinical trials in support of the drug's imminent production. Then, someone in the Indian Council of Medical Research (ICMR) raised an alarm that Risug led to higher levels of albumin in urine. Guha countered with evidence that albumin levels in men increased across the hot, thirsty months of the Indian summer, when the heat robs bodies of vital nutrients. There was also another problem. In the early 2000s, the Indian government set about tightening the rules for drug approvals among other intellectual property (IP) rights requirements. The timeline granted under the defining Trade-Related Aspects of Intellectual Property Rights (TRIPs) agreement of the World Trade Organisation (WTO), framed in 1995 by the WTO's former avatar known as the General Agreement on Tariffs and Trade, was drawing to a close. The ICMR decided to adopt a set of Good Manufacturing Practices (GMP) and Good Laboratory Practices (GLP) for clinical drug trials. Even if there had been a case for allowing Risug to be tested in the older framework of rules, the drug had been discredited. Everything had to start over. At that time, Guha approached then Indian President Abdul Kalam for help. Kalam is a famous orator, known as a man of science himself, having spent his life working for the Indian national program on nuclear weapons. "He told me, 'Sujoy, you know this is not a scientific block. You have to solve this in other ways'," Guha said. Rejection. Anger. Mellowing. Acceptance. "Sir used to say that every invention takes its maker through four stages," said Dr. Sohini Roy, a biologist who did her PhD under Guha and is now a postdoctoral fellow at UCLA. "He prepared us well for life." When Guha and his co-authors published the first paper on Risug in the international research journal Contraception, he was just 40 years old. He was a professor with both the Indian Institute of Technology Delhi and the All India Institute of Medical Sciences (AIIMS), two of the most renowned institutions in the country, and already had the reputation of a maverick. But he was not a medical doctor, and the ICMR would not consider a drug molecule devised by a non-medically trained individual for clinical trials. At the age of 41, Guha took the medical entrance examination for Delhi University and passed. He completed his medical degree studies while continuing to teach electrical engineering at IIT and biomedical engineering at All India Institute of Medical Sciences (AIIMS). When the clinical testing process began, trials on rats and rabbits (smaller animals) and monkeys (larger animals) moved fairly fast and proved successful. Phase-one of the human clinical trials on 17 volunteers was completed in 1993. It went perfectly. Then, someone photocopied sections from a book called Hazardous Chemicals: Desk Reference and sent them to the national research council. The sections in question listed styrene and maleic anhydride, both part of Risug's formulation, as carcinogens. Guha had to counter again: he argued that substances can be individually toxic in nature but harmless as compounds. He gave the example of pure chlorine, which can melt human flesh on its own, but combined with sodium, it becomes sodium chloride, the basic salt that we consume in our diets. When trials did not resume by 1996, the professor petitioned the Supreme Court. The court dismissed Guha's petition in five minutes, saying they were not the competent authority to rule on it. But it seemed to have sent a message to the government. Phase-two resumed. The antagonist in Risug's story is not the Indian government, according to Guha, but the international pharmaceutical lobby. "The government has, in fact, put in a lot of time and money for the clinical trials," he said. "In the first place, there would be no trials without them." Many of the questions raised about Risug and the resultant delays have been instigated by the National Institutes of Health (NIH) in the US, he contends. For several years, the agency wanted to promote a drug for men that involved regular ingestion like the female pill, Guha said. The first medical practitioner to administer Risug for clinical trials, Dr Gulshanjit Singh, told me a similar thing some years ago. The NIH, he said, was batting for a hormone-based, repeat-use drug developed by a US-based firm. He remembered meetings where a section of the ICMR argued strongly in favour of this American drug, and pointed out problems with Risug. Singh served as the head of the department of surgery in Safdarjung Hospital and Deen Dayal Upadhyay hospital, two prestigious publicly-funded hospitals in New Delhi. Recent developments seem to support this claim. The drug whose trials were stopped in October 2016 was a hormone-based solution, relying on regular ingestion to control the production of hormones. Regular use implies long-term sales, a steady guarantee of profit. Risug, on the other hand, requires a maximum of two doses--one injection to put the polymer film in place, and another to flush it out of the vas deferens. "In fact, even in the World Health Organization (WHO), there are people who don't want the drug [Risug] to come through," A.R. Nanda, the Union health secretary from 1999-2002, told me. Then, in 2002 came the albumin charge that halted Risug trials, and subsequently the ICMR decided to put Risug through the new framework for clinical drug trials. The clock turned back to the start. Soon after 2002, the professor came away to IIT Kharagpur. He had enrolled in the seventh batch of IIT Kharagpur in 1957. It was the first IIT to be established in India--the first child of prime minister Jawaharlal Nehru's technology-centric national project--and when the professor attended, it was still suffused with a romantic sense of national service. Here in Kharagpur, he established the Risug Center With a new batch of students and researchers. This includes a laboratory, where they produce the drug used in the clinical trials of Risug. When the approval comes through, Guha's team has the knowhow to scale up from the few hundred units they currently produce, to several thousands for market production. There's also another personal history: his maternal uncle was imprisoned for eight years (in three separate terms) by the British colonial administration at the infamous Hijli detention camp here. But he survived it. "From my mother's side of the family, I get my obstinacy. And my father, I saw him kill himself looking after his patients in Patna [the capital of Bihar]. I learned how to keep a job from him," he said. Guha is both a good storyteller, frank without being self-deprecating, realistic and philosophical. He rarely answers a question when you ask it; he gives every question thought and more often than not, he decides it's not worth his time to answer. It takes a certain kind of temper to be a scientist in the Third World. To not be worn out by the waiting, and form-filling, and inevitable jealousies--among peers, bureaucrats, and scientists in other countries. Guha knows this. He makes sure to sleep. He jogs every night because it makes him feel like himself. He tucks his shirt in and combs his silver hair carefully. When I asked Guha if he felt more anxious now than he had in 2002, he walked ahead of me without answering. I thought he wasn't going to answer, but he turned around some seconds later. "One hopes that I have learnt something. I am no longer an angry man." A longer profile of Prof Guha and Risug was published in The Wire .
Gauresh V.,Safdarjung Hospital
Chinese Journal of Traumatology - English Edition | Year: 2014
Objective The rapid expansion of knowledge regarding the functional anatomy of hand and wrist, increasing functional demands of senior citizens and improved methodologies of achieving and maintaining anatomic restoration of distal radius fractures has generated a renewed interest in addressing these fractures in a more precise manner. The purpose of our study was to evaluate the difference in patients function among those treated by 1) closed reduction and Plaster of Paris cast, 2) distractor application, or 3) open reduction and internal fixation with a volar plate, and to assess the treatment choice for each particular fracture type. Methods A prospective study was carried out on 60 patients with fractures of the distal end radius. Fractures were classified according to the AO classification into type A (extra-articular), type B (partial articular) and type C (complete articular). After initial evaluation patients were taken up for either conservative or operative treatment and were followed up for two years. Results Anatomical results were evaluated according to the Sarmiento's modification of Lindstrom Criteria, which showed that excellent results were more frequent with open reduction and internal fixation using the plating technique. Clinical and functional results were evaluated according to the demerit point system of Gartland and Werley with Sarmiento modification, which was revealed to relate with the type of treatment techniques. Conclusion There is no customized solution for all the fractures of the distal radius. The choice of treatment should be based on the fracture type, the patient's characteristics, the patient's demands and the treating surgeon's experience and preference. © 2014 Daping hospital and the Research Institute of Surgery of the Third Military Medical University.
Dabre K.V.,Commerce and Science College |
Dhoble S.J.,Rashtrasant Tukadoji Maharaj Nagpur University |
Lochab J.,Safdarjung Hospital
Journal of Luminescence | Year: 2014
The Ce3+ doped and undoped samples of alkali earth metal tungstate MWO4 (M=Ca, Sr, and Ba) phosphors are synthesized by a co-precipitation method in controlled pH environment. The resulting phosphors were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), photoluminescence (PL) and thermoluminescence (TL). XRD pattern and SEM micrographs reveal the formation of agglomerated microcrystalline phosphor. FTIR spectra show the strong absorption around 821 cm-1 due to characteristic vibrations of (WO 4)2- complex. PL excitation spectra show broadband in the UV region having peak at 280 nm, and the emission spectrum shows broadband in the visible region with peak in the blue region. The PL emission intensity increases with Ce3+ concentration with the most effective concentration at 5 mol%. The complex TL glow curve of Ce3+ doped phosphors is deconvoluted by using a TLAnal computer program. The trap parameters obtained by TLAnal were compared with those calculated by Chen's method and a possible model for TL is discussed. © 2014 Elsevier B.V.
Saini C.,Safdarjung Hospital Campus |
Ramesh V.,Safdarjung Hospital |
Nath I.,Safdarjung Hospital Campus
PLoS Neglected Tropical Diseases | Year: 2014
Background:Lepromatous leprosy caused by Mycobacterium leprae is associated with antigen specific T cell unresponsiveness/anergy whose underlying mechanisms are not fully defined. We investigated the role of CD25+FOXP3+ regulatory T cells in both skin lesions and M.leprae stimulated PBMC cultures of 28 each of freshly diagnosed patients with borderline tuberculoid (BT) and lepromatous leprosy (LL) as well as 7 healthy household contacts of leprosy patients and 4 normal skin samples.Methodology/Principle Findings:Quantitative reverse transcribed PCR (qPCR), immuno-histochemistry/flowcytometry and ELISA were used respectively for gene expression, phenotype characterization and cytokine levels in PBMC culture supernatants. Both skin lesions as well as in vitro antigen stimulated PBMC showed increased percentage/mean fluorescence intensity of cells and higher gene expression for FOXP3+, TGF-β in lepromatous (p<0.01) as compared to tuberculoid leprosy patients. CD4+CD25+FOXP3+ T cells (Tregs) were increased in unstimulated basal cultures (p<0.0003) and showed further increase in in vitro antigen but not mitogen (phytohemaglutinin) stimulated PBMC (iTreg) in lepromatous as compared to tuberculoid leprosy patients (p<0.002). iTregs of lepromatous patients showed intracellular TGF-β which was further confirmed by increase in TGF-β in culture supernatants (p<0.003). Furthermore, TGF-β in iTreg cells was associated with phosphorylation of STAT5A. TGF-β was seen in CD25+ cells of the CD4+ but not that of CD8+ T cell lineage in leprosy patients. iTregs did not show intracellular IFN-γ or IL-17 in lepromatous leprosy patients.Conclusions/Significance:Our results indicate that FOXP3+ iTregs with TGF-β may down regulate T cell responses leading to the antigen specific anergy associated with lepromatous leprosy. © 2014 Saini et al.
Kakkar A.K.,Safdarjung Hospital |
Dahiya N.,Lady Hardinge Medical College
European Journal of Internal Medicine | Year: 2015
Obesity is a growing epidemic and a major contributor to the global burden of disease. Obesity strains the healthcare systems and has profound economic and psychosocial consequences. Historically, pharmacotherapy for obesity has witnessed the rise and fall of several promising drug candidates that had to be eventually withdrawn due to unacceptable safety concerns. Currently four drugs are approved for chronic weight management in obese adults: orlistat, lorcaserin, phentermine/topiramate extended release and naltrexone/bupropion extended release. While lorcaserin and phentermine/topiramate were approved by US Food and Drug Administration (FDA) in 2012, after a gap of 13 years following the licensing of orlistat, naltrexone/bupropion has been recently approved in 2014. This review provides a brief overview of these current therapeutic interventions available for management of obesity along with the evidence of their safety and efficacy. Additionally, several novel monotherapies as well as combination products are undergoing evaluation in various stages of clinical development. These therapies if proven successful will strengthen the existing armamentarium of antiobesity drugs and will be critical to combat the global public health crisis of obesity and its associated co-morbidities. © 2015 European Federation of Internal Medicine. All rights reserved.
Kakkar A.K.,Safdarjung Hospital |
Dahiya N.,Lady Hardinge Medical College
European Journal of Pharmacology | Year: 2015
Parkinson's disease (PD) is chronic progressive neurodegenerative disorder characterized by profound loss of dopaminergic neurons in the nigrostriatal pathway. It is recognized by the cardinal clinical features of bradykinesia, rigidity, tremor and postural instability. Current therapeutic options are primarily dopamine replacement strategies that only provide symptomatic improvement without affecting progressive neuronal loss. These treatments often fail to provide sustained clinical benefit and most patients develop motor fluctuations and dyskinesias as the disease progresses. Additionally, non-motor symptoms such as autonomic disturbances, sensory alterations, olfactory dysfunction, mood disorders, sleep disturbances and cognitive impairment cause considerable functional disability in these patients and these features often fail to respond to standard dopaminergic treatments. This mini review outlines the current pharmacotherapeutic options for PD and highlights the emerging experimental therapies in various phases of clinical development. © 2015 Elsevier B.V. All rights reserved.
Sethuraman G.,All India Institute of Medical Sciences |
Ramesh V.,Safdarjung Hospital
Pediatric Dermatology | Year: 2013
Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis that accounts for 1% to 2% of cases. Childhood skin tuberculosis represents 18% to 82% of all cutaneous tuberculosis cases. Scrofuloderma and lupus vulgaris are the two most common clinical forms in children. An increase in the number of tuberculids, especially lichen scrofulosorum, has been observed in the last several years. Cutaneous tuberculosis in children can be severe and have a protracted course. Multiplicity of lesions and multifocal disseminated involvement in scrofuloderma and lupus vulgaris is common. Scrofuloderma progressing to gummatous lesions (scrofulous gumma) is mostly described in children. Morbidities and deformities are more severe in children. © 2012 Wiley Periodicals, Inc.
Nanda S.,Safdarjung Hospital |
Bansal S.,Safdarjung Hospital
Indian Journal of Dermatology, Venereology and Leprology | Year: 2013
The demand for facial rejuvenation is increasing, with each passing day, in all age groups. A number of procedures like chemical peels, microdermabrasion, laser and light therapies, and minimally invasive procedures like botulinum toxin injections (BTX A) and hyaluronic acid (HA) fillers are being extensively used by the dermatologist and plastic surgeons to meet this growing demand. A good knowledge of use of these techniques is becoming imperative for the dermatologist. In the present article, we discuss in detail the use of botulinum toxin injections and hyaluronic acid fillers for rejuvenation of upper face. Special emphasis has been placed on the complications associated with treatment of each area and on how to manage the same.
Mehta A.K.,Safdarjung Hospital |
Tripathi C.D.,Safdarjung Hospital
Nutritional Neuroscience | Year: 2015
Objective: The management of neuropathic pain remains unsatisfactory till date, despite immense advances in the therapeutic strategies. Commiphora mukul (CM), also known as Commiphora wightii, is well known in the traditional Indian system of medicine, and has been used to treat ailments such as obesity, bone fractures, arthritis, inflammation, cardiovascular diseases, and lipid disorders. The present study was performed to investigate the effect of CM on peripheral neuropathic pain in rats. Methods: Neuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, CM was orally administered for 2 weeks in doses of 50, 100, and 200 mg/kg, and pain assessment was performed by employing the behavioral tests for thermal hyperalgesia (hot-plate and tail-flick tests) and cold allodynia (acetone test). Results: Following the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of CM (50 mg/kg) did not have any effect on the hotplate and tail-flick tests, but significant anti-allodynic effect was observed in the acetone test. Furthermore, administration of CM (100 mg/kg) caused significant decrease in pain as observed on the tail-flick and acetone tests, but not in the hot-plate test. CM in a dose of 200 mg/kg significantly modulated neuropathic pain as observed from the increased hot-plate and tail-flick latencies, and decreased paw withdrawal duration (in acetone test). Discussion: Therefore, the present study suggests that CM may be used in future as a treatment option for neuropathic pain. © 2015 W.S.Maney & Son Ltd.
Sharda N.,Safdarjung Hospital
Cardiology in the Young | Year: 2014
Cardiac involvement is a rare initial presentation of systemic lupus erythematosus. An 11-year-old girl was described to have massive haemorrhagic pericardial effusion and cardiac tamponade, which was later diagnosed as systemic lupus erythematosus. Therefore, in children presenting with cardiac tamponade, systemic lupus erythematosus should be considered as one of the differential diagnoses, as morbidity and mortality associated with cardiac tamponade can be dramatically reduced with early diagnosis and use of steroids. © 2013 Cambridge University Press.