Browsing by Author "Antony, Aśok C."

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    Clinical conundrum: managing iron overload after renal transplantation
    (BMJ, 2021-02-05) Upadhyay, Binayak; Green, Steven D.; Khanal, Nabin; Antony, Aśok C.; Medicine, School of Medicine
    Iatrogenic iron overload, which is not uncommon in patients undergoing long-term haemodialysis, arises from a combination of multiple red cell transfusions and parenteral iron infusions that are administered to maintain a haemoglobin concentration of approximately 10 g/dL. Although iron overload due to genetic haemochromatosis is conventionally managed by phlebotomy, patients with haemoglobinopathies and chronic transfusion-induced iron overload are treated with iron-chelation therapy. However, the management of iron overload in our patient who presented with hepatic dysfunction and immunosuppressive drug-induced mild anaemia in the post-renal transplant setting posed unique challenges. We report on the decision-making process used in such a case that led to a successful clinical resolution of hepatic iron overload through the combined use of phlebotomy and erythropoiesis stimulating agents, while avoiding use of iron-chelating agents that could potentially compromise both hepatic and renal function.
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    Evidence for potential underestimation of clinical folate deficiency in resource-limited countries using blood tests
    (Oxford, 2017-08) Antony, Aśok C.; Medicine, School of Medicine
    Although a low serum folate concentration is a useful biomarker of pure folate deficiency, the presence of vitamin B12 deficiency or hemolysis or both in individuals with low folate status predictably raises serum folate levels. Therefore, in resource-limited settings where dietary folate deficiency can coexist with vitamin B12 deficiency or malaria or both, the serum folate concentration can range from normal to high, leading to serious underestimation of tissue folate status. This review traces the genesis of an inappropriate overreliance on the serum folate concentration to rule out folate deficiency in vulnerable populations of women and children. Of significance, without due consideration of a chronically inadequate dietary folate intake, authors of influential studies have likely wrongly judged these populations to have an adequate folate status. Through repetition, this error has led to a dangerous entry into the contemporary medical literature that folate deficiency is rare in women and children. As a consequence, many millions of under-resourced women and children with mild to moderate tissue folate deficiency may have been deprived of folate replacement. This review uses historical documents to challenge earlier conclusions and re-emphasizes the need for contextual integration of clinical information in resource-limited settings.
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    Folate Deficiency Facilitates Genomic Integration of Human Papillomavirus Type 16 DNA In Vivo in a Novel Mouse Model for Rapid Oncogenic Transformation of Human Keratinocytes
    (Oxford, 2018) Xiao, Suhong; Tang, Ying-Sheng; Kusumanchi, Praveen; Stabler, Sally P.; Zhang, Ying; Antony, Aśok C.; Medicine, School of Medicine
    Background Epidemiologic and in vitro studies suggest independent linkages between poor folate and/or vitamin B-12 nutrition, genomic human papillomavirus (HPV) type 16 viral integration, and cancer. However, there is no direct evidence in vivo to support the causative role of poor folate nutrition in HPV16 integration into the cellular genome. Objective We tested the hypothesis that folate deficiency enables the integration of HPV16 into the genome of HPV16-harboring keratinocytes, and could thereby influence earlier transformation of these cells to cancer in an animal model. Methods HPV16-harboring human keratinocytes [(HPV16)BC-1-Ep/SL] were differentiated into 3-dimensional HPV16-organotypic rafts under either folate-replete or folate-deficient conditions in vitro. These were then subcutaneously implanted in severely immunocompromised female Beige Nude XID (Hsd: NIHS-LystbgFoxn1nuBtkxid) mice (4–6 wk old, 16–18 g) fed either a folate-replete diet (1200 nmol folate/kg diet) or a progressively folate-deficient diet (600 or 400 nmol folate/kg diet) for 2 mo prior to raft-implantation surgery, and indefinitely thereafter. The tumors that subsequently developed were characterized for onset, pattern of growth, morphology, HPV16 oncogene expression, and HPV16-genomic integration. Results All HPV16-organotypic rafts developed in either folate-replete or physiologic low-folate media in vitro and subsequently implanted in folate-replete mice eventually transformed into aggressive malignancies within weeks. When compared to HPV16-high folate-organotypic raft-derived tumors from mice fed either a 1200 or 600 nmol folate/kg diet, those raft-derived cancers that developed in mice fed a 400 nmol folate/kg diet expressed significantly more HPV16 E6 (1.8-fold more) and E7 (2.8-fold more) oncogenic proteins (P = 0.001), and revealed significantly more HPV16-integration sites in genomic DNA (2-fold more), either directly into, or in the vicinity of, cellular genes (P < 0.05). Conclusions This unprecedented animal model for the consistent rapid transformation of differentiated (HPV16)BC-1-Ep/SL-derived organotypic raft-keratinocytes to cancer in Beige Nude XID mice confirms that dietary folate deficiency can profoundly influence and modulate events leading to HPV16-induced carcinogenesis, and facilitates genomic integration of HPV16 DNA in vivo.
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    Potential for elimination of folate and vitamin B12 deficiency in India using vitamin-fortified tea: a preliminary study
    (BMJ, 2021-06-23) Vora, Ravindra M.; Alappattu, Meryl J.; Zarkar, Apoorva D.; Soni, Mayur S.; Karmarkar, Santosh J.; Antony, Aśok C.; Medicine, School of Medicine
    Introduction: The majority of Indian women have a poor dietary folate and vitamin B12 intake resulting in their chronically low vitamin status, which contributes to anaemia and the high incidence of folate-responsive neural-tube defects (NTDs) in India. Although many countries have successfully deployed centrally-processed folate-fortified flour for prevention of NTDs, inherent logistical problems preclude widespread implementation of this strategy in India. Because tea-the second most common beverage worldwide (after water)-is consumed by most Indians every day, and appeared an ideal vehicle for fortification with folate and vitamin B12, we determined if daily consumption of vitamin-fortified tea for 2 months could benefit young women of childbearing-age in Sangli, India. Methods: Women (average age=20±2 SD) used teabags spiked with therapeutic doses of 1 mg folate plus either 0.1 mg vitamin B12 (Group-1, n=19) or 0.5 mg vitamin B12 (Group-2, n=19), or mock-fortified teabags (Group-0, n=5) to prepare a cup of tea every day for 2 months, following which their pre-intervention and post-intervention serum vitamin and haemoglobin concentrations were compared. Results: Most women had baseline anaemia with low-normal serum folate and below-normal serum vitamin B12 levels. After 2 months, women in both Group-1 and Group-2 exhibited significant increases in mean differences in pre-intervention versus post-intervention serum folate levels of 8.37 ng/mL (95% CIs 5.69 to 11.04, p<0.05) and 6.69 ng/mL (95% CI 3.93 to 9.44, p<0.05), respectively; however, Group-0 experienced an insignificant rise of 1.26 ng/mL (95% CI -4.08 to 0.16). In addition, over one-half and two-thirds of women in Group-1 and Group-2, respectively, exhibited increases in serum vitamin B12 levels over 300 pg/mL. There was also a significant post-interventional increase in the mean haemoglobin concentration in Group-1 of 1.45 g/dL (95% CI 0.64 to 2.26, p=0.002) and Group-2 of 0.79 g/dL (95% CI 0.11 to 1.42, p=0.027), which reflected a bona fide clinical response. Conclusion: Tea is an outstanding scalable vehicle for fortification with folate and vitamin B12 in India, and has potential to help eliminate haematological and neurological complications arising from inadequate dietary consumption or absorption of folate and vitamin B12.
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    The silent tragic reality of Hidden Hunger, anaemia, and neural-tube defects (NTDs) in India
    (Elsevier, 2022-11) Antony, Aśok C.; Vora , Ravindra M.; Karmarkar, Santosh J.; Medicine, School of Medicine
    Hidden Hunger arising from nutritional iron-, folate-, and vitamin-B12-deficiencies is exceedingly common in India and has profound negative impacts on anaemia, on pregnancy, and on embryonic-foetal neurodevelopment in utero, which predisposes to NTDs and psychological-psychiatric manifestations in childhood. Whereas younger-to-middle-aged Indians fail to perform at maximum potential, the elderly are at risk for calamitous neurologic events. However, these micronutrient-deficiencies are eminently correctable through food-fortification. Therefore, the Indian Government can no longer afford the luxury of inaction by either denying or downplaying the gravity of this problem. What is critically needed from India's leaders is an urgent, clear-eyed reappraisal and act of anagnorisis—(an often startling self-recognition and discovery of a profoundly serious error and tragic flaw)—in failing to confront this problem for decades. Only when closely followed by a metanoia—(a transformative change of heart that triggers remedial action)—can they help India avoid a catastrophic tryst with destiny.
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    The silent tragic reality of Hidden Hunger, anaemia, and neural-tube defects (NTDs) in India
    (Elsevier, 2022-09-17) Antony, Aśok C.; Vora, Ravindra M.; Karmarkar, Santosh J.; Medicine, School of Medicine
    Hidden Hunger arising from nutritional iron-, folate-, and vitamin-B12-deficiencies is exceedingly common in India and has profound negative impacts on anaemia, on pregnancy, and on embryonic-foetal neurodevelopment in utero, which predisposes to NTDs and psychological-psychiatric manifestations in childhood. Whereas younger-to-middle-aged Indians fail to perform at maximum potential, the elderly are at risk for calamitous neurologic events. However, these micronutrient-deficiencies are eminently correctable through food-fortification. Therefore, the Indian Government can no longer afford the luxury of inaction by either denying or downplaying the gravity of this problem. What is critically needed from India's leaders is an urgent, clear-eyed reappraisal and act of anagnorisis—(an often startling self-recognition and discovery of a profoundly serious error and tragic flaw)—in failing to confront this problem for decades. Only when closely followed by a metanoia—(a transformative change of heart that triggers remedial action)—can they help India avoid a catastrophic tryst with destiny.