Risk of Carcinogenicity Associated with Synthetic Hair Dyeing Formulations: A Biochemical View on Action Mechanisms, Genetic Variation and Prevention.

Article tries to visualize the potential for carcinogenic trigger in humans with a preference for oxidative synthetic of hair dyeing formulations, especially which belong to the category of permanent colours. According to the International Agency for Cancer, hair dyes for personal use are not strictly classified as carcinogen to humans. However, some controversy exists that requires clarification. Some epidemiological studies support the association between the risk of cancer development and personal use of hair dyes (pooled relative risk RR = 1.50. 95% CI: 1.30-1.98). The world-wide sale of hair dyeing cosmetics have exceeded 15 billion dollars by the year 2012 and has maintained an annual growth rate of 8-10%. This raises concerns and need to be addressed. The review article briefly discusses about the different hair dye components based on their chemical nature, permanence, interaction of dye components with different parts of the hair shaft, action mechanisms, health risk assessment, associated challenges and possible alternatives. There appears variability towards the pathological changes incurred in the human system upon the use of synthetic hair formulations. This probably appears due to the presence of interindividual genetic variation of enzymes handling these xenobiotics. The redox mechanism of major hair dye components appears to be involved in the carcinogenic trigger. Most of the hair dye constituents pose serious health issues. However, we do have few better alternatives to prevent the toxicity associated with hair dye constituents without compromising the need of today's fashion statement and expectations of the youth.

Burden and cost of communicable, maternal, perinatal and nutrition deficiency diseases in India.

BACKGROUND: Globally 36% of deaths and 42% of Disability Adjusted Life Years (DALYs) are due to communicable, maternal, perinatal and nutritional disorders (CMPND). We examined the state-wise disease burden and treatment cost for these diseases in India for 2017. METHODS: DALYs for CMPND was obtained from National Disease Burden Estimate (NBE) Study and the expenditure was determined from the unit level records of persons who reported hospitalization for one or more CMPND in National Sample Survey (NSS)-75th Round. RESULTS: The top conditions resulting in high DALYs for India were perinatal conditions and nutritional deficiency disorders. Odisha had the highest DALY rate, while Kerala had the lowest DALY rate for CMPNDs. The out-of-pocket expenditure (OOPE) was highest in Chattisgarh, while percentage of households pushed to CHE was highest in Uttar Pradesh for CMPND. CONCLUSION: The public healthcare facilities need to be strengthened to facilitate patients with CMPND to undergo treatment that is timely, affordable and cost-effective. Efforts should be made for optimization of strategies aimed at primary and secondary prevention of CMPND and reduce OOPE for treatment of these diseases. In addition, advocacy spreading awareness will reduce the burden and treatment expenditure for CMPNDs in India.

Rising healthcare expenditure on tuberculosis: Can India achieve the End TB goal?

OBJECTIVE: To examine the out-of-pocket expenditure (OOPE), healthcare burden, catastrophic health expenditure, hardship financing and impoverishment effects of TB treatment in India. METHODS: Data of three rounds of National Statistic Surveys 60th 2004-05, 71st 2013-14 and 75th 2017-18. Descriptive statistics, bivariate estimates and multivariate models were performed to calculate the OOPE, healthcare burden, catastrophic health expenditure, hardship financing and impoverishment using standard definitions at December 2019 price values. RESULTS: More than two-thirds of the TB cases are seen in the economically productive age group (14-59 years). Illiterate patients had a higher healthcare burden and OOPE. The healthcare burden, hardship financing and catastrophic health expenditure are considerably higher for those utilising private hospitals. Male patients have a higher exposure to hardship financing than female patients. Impoverishment effects are higher among Hindus and illiterate populations due to utilisation of hospitalisation services. CONCLUSION: The present analysis helps to understand the trends in the financial burden of TB on households over last 15 years, thus providing evidence to policymakers for more effective channelling of resources in order to achieve a TB-free India by 2025.

Socioeconomic Impact of Hospitalization Expenditure for Treatment of Noncommunicable Diseases in India: A Repeated Cross-Sectional Analysis of National Sample Survey Data, 2004 to 2018.

OBJECTIVES: This article explores the consequences of hospitalization expenditure on noncommunicable diseases (NCD) and its impact on out-of-pocket expenditure (OOPE), catastrophic health expenditure, impoverishment, and hardship financing of households in India. METHODS: Data on hospitalized cases of NCDs from the 3 rounds of National Sample Surveys (NSS) (2004, 2014, 2018) were used. Bivariate and multivariate analyses were conducted to investigate the socioeconomic differentials of the impact of OOPE on catastrophic health expenditure, impoverishment, and exposure to hardship financing. RESULTS: Rural households had greater exposure to catastrophic health expenditure but urban households had higher risk of impoverishment due to OOPE. Older patients (aged ≥60 years) had the highest hospitalization rate per 100 000, including increase in average healthcare expenditure from 2004 to 2018. At 10% and 30% thresholds, 50% and 25% of the households, respectively, faced catastrophic health expenditure across all the 3 rounds. Due to OOPE on hospitaliation treatment for NCDs, about 3.8%, 7.4% and 4.8% of households fell below poverty line, and percentage shortfall in income for the population from the poverty line was 3%, 4.9% and 3%, in 2004, 2014 and 2018 respectively. Percentage of households facing hardship financing reduced from 49.2% in 2004 to 24.4% 2014 and 12.7% in 2018. CONCLUSION: OOPE by households are still very high and hence the higher effects of CHE, impoverishment and exposure to hardship financing due to health expenditure in India. This study proposes that along with increase in budgetary allocations for healthcare, the government should develop suitable policies to expand the effectiveness of government-sponsored health insurance, such as developing a specific NCD service package to be included in the health insurance program.

Levels of anti-fructose-modified HSA antibodies correlate with disease status in diabetic subjects.

OBJECTIVE: This study aimed to assess the changes induced in HSA upon fructose-modification and to use the modified protein as an antigen for studying the presence of antibodies in diabetic patients. Further, magnitude of oxidative stress was also assessed. METHODS: HSA was modified with fructose, changes induced were studied by DSC measurements and near-UV CD. The binding characteristics of antibodies in the sera of diabetes patients to native and modified-HSA was assessed by ELISA and band shift assay. The oxidative stress in these patients was studied by carbonyl content estimation, FRAP assay and TBARS determination RESULTS: DSC revealed that fructose modified-HSA was more thermostable than its native form. Changes in tertiary structure of fructose-modified HSA were seen in near-UV CD. Patient studies showed that fructose-modified HSA acts as a potent immunogen compared to its native form and the levels of antibodies against fructose-modified HSA served as a parameter for tracking the glycemic control and oxidative stress parameters (carbonyl content, FRAP value and MDA level) in diabetic patients. CONCLUSIONS: Fructose-modification of HSA causes perturbations in its structure and function, thereby, making the protein antigenic besides decreasing its antioxidant capacity. This study suggests that fructose-modified-HSA is an important contributor in diabetic pathophysiology.

Fructosylation generates neo-epitopes on human serum albumin.

Hyperglycemia is the defining feature of diabetes mellitus. The persistently high levels of reducing sugars like glucose and fructose cause glycation of various macromolecules in the body. Human serum albumin (HSA), the most abundant serum protein with a myriad of functions, is prone to glycation and consequent alteration in its structural and biological properties. This study aimed to assess the role of fructose-modified human serum albumin as a marker of diabetic pathophysiology. We carried out modification of HSA with fructose and the changes induced were studied by various physicochemical studies. Fructose modified-HSA showed hyperchromicity in UV spectrum and increased AGE-specific fluorescence as well as quenching of tryptophan fluorescence. In SDS-PAGE protein aggregation was seen. Amadori products were detected by NBT. The fructose modified HSA had higher content of carbonyls along with perturbations in secondary structure as revealed by CD and FT-IR. A greater hydrodynamic radius of fructose-modified HSA was evident by DLS measurement. The fructose-modified HSA induced high titre antibodies in experimental animals exhibiting high specificity towards the immunogen.

Preferential recognition of peroxynitrite-modified human serum albumin by circulating autoantibodies in cancer.

Peroxynitrite is a potent oxidizing and nitrating agent and has in vivo existence. Several studies have shown the damaging role of this molecule in biological system. Human serum albumin (HSA), being most abundant plasma protein, is easily targeted by different oxidizing and nitrating agents. Free radicals increase the onset of different cancers as evident by several researchers. In the present study, structural perturbations in HSA by peroxynitrite were observed by MALDI-MS, DSC and DLS. Immunological studies showed enhanced binding of peroxynitrite-modified HSA with cancer autoantibodies, compared to the native protein. A decline in the antioxidant property of peroxynitrite-modified HSA was also observed. Therefore, we may conclude that peroxynitrite exposure results in structural alteration and hence generation of neo-epitopes in HSA molecule along with the decrease in its antioxidant property. The possible role of peroxynitrite-modified HSA in carcinogenesis has been discussed.

Pathophysiological Role of Peroxynitrite Induced DNA Damage in Human Diseases: A Special Focus on Poly(ADP-ribose) Polymerase (PARP).

Peroxynitrite is formed in biological systems when nitric oxide and superoxide rapidly interact at near equimolar ratio. Peroxynitrite, though not a free radical by chemical nature, is a powerful oxidant which reacts with proteins, DNA and lipids. These reactions trigger a wide array of cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. The present review outlines the various peroxynitrite-induced DNA modifications with special mention to the formation of 8-nitroguanine and 8-oxoguanine as well as the induction of DNA single strand breakage. Low concentrations of peroxynitrite cause apoptotic death, whereas higher concentrations cause necrosis with cellular energetics (ATP and NAD(+)) serving as control between the two modes of cell death. DNA damage induced by peroxynitrite triggers the activation of DNA repair systems. A DNA nick sensing enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) becomes activated upon detecting DNA breakage and it cleaves NAD(+) into nicotinamide and ADP-ribose and polymerizes the latter on nuclear acceptor proteins. Over-activation of PARP induced by peroxynitrite consumes NAD(+) and consequently ATP decreases, culminating in cell dysfunction, apoptosis or necrosis. This mechanism has been implicated in the pathogenesis of various diseases like diabetes, cardiovascular diseases and neurodegenerative diseases. In this review, we have discussed the cytotoxic effects (apoptosis and necrosis) of peroxynitrite in the etiology of the mentioned diseases, focusing on the role of PARP in DNA repair in presence of peroxynitrite.