A Delphi consensus on the nomenclature and diagnosis of lichen planus pigmentosus and related entities

Background: Although well known in clinical practice, research in lichen planus pigmentosus and related dermal pigmentary diseases is restricted due to lack of consensus on nomenclature and disease definition. Aims and Objectives: Delphi exercise to define and categorise acquired dermal pigmentary diseases. Methods: Core areas were identified including disease definition, etiopathogenesis, risk factors, clinical features, diagnostic methods, treatment modalities and outcome measures. The Delphi exercise was conducted in three rounds. Results: Sixteen researchers representing 12 different universities across India and Australia agreed to be part of this Delphi exercise. At the end of three rounds, a consensus of >80% was reached on usage of the umbrella term ‘acquired dermal macular hyperpigmentation’. It was agreed that there were minimal differences, if any, among the disorders previously defined as ashy dermatosis, erythema dyschromicum perstans, Riehl’s melanosis and pigmented contact dermatitis. It was also agreed that lichen planus pigmentosus, erythema dyschromicum perstans and ashy dermatosis did not differ significantly apart from the sites of involvement, as historically described in the literature. Exposure to hair colours, sunlight and cosmetics was associated with these disorders in a significant proportion of patients. Participants agreed that both histopathology and dermatoscopy could diagnose dermal pigmentation characteristic of acquired dermal macular hyperpigmentation but could not differentiate the individual entities of ashy dermatosis, erythema dyschromicum perstans, Riehl’s melanosis, lichen planus pigmentosus and pigmented contact dermatitis. Limitations: A wider consensus involving representatives from East Asian, European and Latin American countries is required. Conclusion: Acquired dermal macular hyperpigmentation could be an appropriate conglomerate terminology for acquired dermatoses characterised by idiopathic or multifactorial non-inflammatory macular dermal hyperpigmentation

Clinical characteristics & outcome of SARS-CoV-2 infected neonates presenting to paediatric emergency

Background & objectives: Data on neonatal COVID-19 are limited to the immediate postnatal period, with a primary focus on vertical transmission in inborn infants. This study was aimed to assess the characteristics and outcome of COVID-19 in outborn neonates. Methods: All neonates admitted to the paediatric emergency from August 1 to December 31, 2020, were included in the study. SARS-CoV-2 reverse transcription- (RT)-PCR test was done on oro/nasopharyngeal specimens obtained at admission. The clinical characteristics and outcomes of SARS-CoV-2 positive and negative neonates were compared and the diagnostic accuracy of a selective testing policy was assessed. Results: A total of 1225 neonates were admitted during the study period, of whom SARS-CoV-2 RT-PCR was performed in 969. The RT-PCR test was positive in 17 (1.8%). Mean (standard deviation) gestation and birth weight of SARS-CoV-2-infected neonates were 35.5 (3.2) wk and 2274 (695) g, respectively. Most neonates (11/17) with confirmed COVID-19 reported in the first two weeks of life. Respiratory distress (14/17) was the predominant manifestation. Five (5/17, 29.4%) SARS-CoV-2 infected neonates died. Neonates with COVID-19 were at a higher risk for all-cause mortality [odds ratio (OR): 3.1; 95% confidence interval (CI): 1.1-8.9, P=0.03]; however, mortality did not differ after adjusting for lethal malformation (OR: 2.4; 95% CI: 0.7-8.7). Sensitivity, specificity, accuracy, positive and negative likelihood ratios (95% CI) of selective testing policy for SARS-CoV-2 infection at admission was 52.9 (28.5-76.1), 83.3 (80.7-85.6), 82.8 (80.3-85.1), 3.17 (1.98-5.07), and 0.56 (0.34-0.93) per cent, respectively. Interpretation & conclusions: SARS-CoV-2 positivity rate among the outborn neonates reporting to the paediatric emergency and tested for COVID-19 was observed to be low. The selective testing policy had poor diagnostic accuracy in distinguishing COVID-19 from non-COVID illness.

Outpatient prescription audit in a tertiary care hospital at Puducherry

Background: Rational use of medicines promotes good health practices and prevents inappropriate use of medicines, polypharmacy, unnecessary use of antimicrobials, injections, and also encourages use of medicines from essential medicine list and dispensing by generic names. The aim of the study was to analyze the outpatient prescriptions of a tertiary care centre by utilizing World Health Organization (WHO) core drug use prescribing indicators.Methods: A retrospective observational study was conducted in a tertiary care health setup at Puducherry, South India. Outpatient prescriptions from all the major clinical departments were analyzed using WHO prescribing indicators and they were compared with some similar studies.Results: The average number of drugs per prescription was 2.74. The percentage of prescriptions with antibiotics was 20.33% and the percentage of prescriptions with injections was 0.16%. The percentage of drugs prescribed by generic names and from essential medicine list was 83.13% and 87.9 respectively. Further antibiotic utilization was found to be higher in the department of ENT (56.67%), respiratory medicine (45%) and surgery (40%). Percentage of drugs prescribed by generic names in pediatrics and respiratory medicine were found to be 67.88% and 65.27% and percentage of drugs prescribed from essential medicine list in dermatology was 69.62%.Conclusions: Prescription pattern followed in our Institute almost adheres to the guidelines laid down by the WHO. Moreover, it is also implied that a routine audit of this type should be done in health care setups to ensure that they adhere to the WHO guidelines for better health care.

Drug Utilization Evaluation Of Benzodiazepines In A Tertiary Care Hospital

Objective: To assess the rationale use of benzodiazepines among various departments in a multi-speciality hospital. Methods: A prospective study was conducted with a sample size of 200 for a period of six months. Data was collected from patients based on inclusion and exclusion criteria. Naranjo Adverse Drug Reaction Probability Scale and Drug Interaction Probability Scale (DIPS) were used as a study tool to measure the causality of adverse drug reactions and drug interactions. Based on the dosage of various benzodiazepines DDD was calculated and compared with WHO Anatomical Therapeutic Chemical (ATC) classification Defined Daily Dose (DDD). Results: BZD’s were mostly prescribed in males (74.5%) and married patients (86.5%) were more exposed to benzodiazepines compared to others. Lorazepam (70.1%) was found to be the most commonly used drug, mainly prescribed for sedation, followed by anxiety. DDD was calculated and majority of patients had DDD in accordance with WHO standard. Based on cost analysis, Clobazam was found to be the high cost and Lorazepam being the low-cost drug. The results of drug utilization evaluation of benzodiazepines study were compiled and reported to the respected department physician and their feedback was collected. Conclusion: The study showed a rational utilization of benzodiazepines and the negative outcomes of BZDs can be reduced by providing drug-related information to the prescribers and consumers.

Effect of secondhand smoke exposure on lung function among non-smoking population

Background: Secondhand Smoke (SHS) exposure is known to be associated with various cardiovascular and respiratory problems but its effect on pulmonary function remains unexplored. This study was done to evaluate the effect of Secondhand Smoke (SHS) exposure on lung function among non-smoking population.Methods: This cross-sectional study was conducted in Bahour, Pondicherry from 2017-2018. 350 participants, age 40 year and older, with no respiratory symptoms or prior lung diseases were included in this study. Both self-reported history and measurement of urinary cotinine level were used to evaluate the smoking status. Spirometry data, including FVC and FEV1 were used to assess lung function. Diverse variables between groups were compared using T- test and Chi-square test. Analysis of covariance (ANCOVA) adjusted for age, height, alcohol consumption, and level of exercise was used to see any statistical differences in lung function parameters between non-SHS exposed and SHS-exposed groups.Results: Among 350 non-smokers, 120 were SHS-exposed. The urinary cotinine levels clearly distinguished SHS exposure, and the mean urinary cotinine levels were 7±0.3 and 11±0.4 in non-SHS exposed group vs SHS-exposed group, respectively. However, both groups had no significant difference in lung function and was found normal.Conclusions: SHS exposure urinary cotinine is a valuable marker.

A cross sectional study on antipsychotic induced amenorrhoea in women attending a tertiary care centre in South India

Background: Absence of menstrual period in a woman of reproductive age group could be physiological or pathological. Ascertaining the cause for this is a common clinical scenario faced by physicians. It is also a common clinical problem in women who are on treatment with antipsychotic medication. This cross-sectional study aimed to assess the occurrence of antipsychotic induced amenorrhoea among women aged 18-45 years, attending outpatient services of a tertiary care setting, the factors associated and to assess the effective strategies of treatment.Methods: Retrospective chart review of clinical details of women in the reproductive age group who fulfilled the inclusion criteria was carried out. They were divided into two groups: Group A included 84 women with antipsychotic induced amenorrhea and Group B included 94 women on antipsychotics and had normal menstrual cycles. Various factors and strategies which worsened or alleviated the symptoms were noted.Results: Women who were less than 35 years of age, on antipsychotic treatment for more than two years duration (52;83.9%) and those who were on treatment with Risperidone (69;73.4%) were identified as having the risk of developing antipsychotic induced amenorrhoea. The strategy of switch of medication to prolactin sparing antipsychotic was more effective in regularising the menstrual cycles (43;87.8%).Conclusions: In women presenting with amenorrhoea, a possible medication induced aetiology need to be considered, especially use of antipsychotics. Further understanding of the complexities of this relationship may help to guide the assessment and proper treatment of women with antipsychotic related amenorrhoea.

Psychotic Symptoms of Hashimoto's Encephalopathy: A Diagnostic Challenge

Hashimoto's encephalopathy (HE) is a rare and underdiagnosed neuropsychiatric illness. We present the case of a 17-year-old girl who was admitted to a tertiary-care psychiatric center with acute onset psychosis and fever. Her psychotic symptoms were characterized by persecutory and referential delusions, as well as tactile and visual hallucinations. Her acute behavioral disturbance warranted admission and treatment in a psychiatric setting (risperidone tablets, 3 mg/day). She had experienced an episode of fever with a unilateral visual acuity defect approximately 3 years before admission, which was resolved with treatment. Focused clinical examination revealed an enlarged thyroid, and baseline blood investigations, including thyroid function test results were normal. Abnormal laboratory investigations revealed elevated anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels (anti-TPO of 480 IU/mL; anti-TG of 287 IU/mL). Results of other investigations for infection, including cerebrospinal fluid examination, electroencephalography, and brain magnetic resonance imaging were normal. She was diagnosed with HE and was treated with intravenous corticosteroids (methylprednisolone up to 1 g/day; tapered and discontinued after a month). The patient achieved complete remission of psychotic symptoms and normalization of the anti-thyroid antibody titers. Currently, at the seventh month of follow-up, the patient is doing well. This case highlights the fact that in the absence of well-defined clinical diagnostic criteria, a high index of suspicion is required for early diagnosis of HE. Psychiatrists need to explore for organic etiologies when dealing with acute psychiatric symptoms in a younger age group.

A cross sectional study to assess clinical profile of acne vulgaris presenting to a tertiary care teaching hospital

Background: Acne is one of the most commonly prevalent skin conditions. It commonly affects the adolescents and young adult age groups. The lesions start as microcomedones and progress to nodular or inflammatory acne with post inflammatory hyperpigmentation. Although acne is not life threatening it has multiple impacts in the affected individual’s quality of life and psychological morale. Hence this study was undertaken to analyze the clinical profile of patients having acne vulgaris to facilitate better management. Materials and methods: A cross sectional observational study was conducted among patients attending the dermatological outpatient department in a tertiary care hospital. A pre-tested semistructured questionnaire was administered to the individuals after obtaining informed written consent. Data on demographical variables, menstrual history and clinical features of acne were collected and presented. Results: A major proportion of the population was comprised of adolescents and young adults similar to previous studies. Around 13% of them had a positive family history of acne. Associated factors such as menstrual flare, increased consumption of dairy products and high glycemic index foods were also present. Almost 88% of the participants had mild acne. Half of them had post inflammatory hyperpigmentation. Conclusions: Most patients of acne vulgaris are either adolescents or young adults. This group is more prone to endocrine co-morbidities such as polycystic ovarian syndrome and impairment in quality of life. Hence considering the above factors, early diagnosis and management of acne vulgaris B.M. Monisha, G. Kannan, Muthusamy. A cross sectional study to assess clinical profile of acne vulgaris presenting to a tertiary care teaching hospital. IAIM, 2018; 5(5): 111-116. Page 112 is essential. This is expected to yield better results in the long term in improving the quality of life in the affected persons

comprehensive review of the diagnosis and management of prosthetic joint infections in the absence of positive cultures

The diagnosis and management of prosthetic joint infections [PJI] with negative cultures remains an enigma without clear definitions and guidelines for its management. In contrast, the literature offers guidelines to the diagnosis and management of culture positive prosthetic joint infections as noted in both the infectious disease literature and the orthopedic literature. This paper outlines the current state of knowledge of PJI with negative cultures and summarizes the recommendations for the work up and management of this condition. In addition, we propose a simple algorithm that clinicians may find useful for the management of PJI with negative cultures. This algorithm has not been validated with data at this point, but can be applied to practice to help direct the management and diagnosis of prosthetic joint infections in the absence of positive cultures

Cytokine gene polymorphisms and their association with cervical cancer: a north Indian study

Introduction: The production of cytokines, growth factors and adhesion molecules promotes tumor progression and involves inflammation, angiogenesis and thrombosis, thus providing optimal conditions for cancer development

Materials and methods: The present study was undertaken to evaluate association of cytokine gene polymorphisms with cervical cancer in a north Indian population. Genotyping of single nucleotide polymorphisms [SNPs] viz. IL-6-597G/A [rs1800797], IL-1[beta]-511C/T [rs16944] and TNF-[alpha]-308G/A [rs1800629] was carried out in 100 each of cases and healthy age matched controls by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]. Genotype and allele frequencies were calculated by SPSS [ver.16] and gene-gene interaction was analyzed using SHEsis [ver. Online]

Results: Epidemiological studies showed that women >40 years have higher risk of cervical cancer due to early pregnancies. IL-6 and TNF-[alpha] promoter polymorphisms showed significant association [P < 0.001] while the SNP combinations G A T[Asterisk] and G G T[Asterisk] of IL-6-597A/G, TNF-[alpha]-308G/ A and IL-1[beta]-511C/T polymorphisms showed increased risk up to 9.0 and 3.30 times respectively

Conclusion:Therefore, the promoter polymorphisms in cytokine genes can be used as biomarkers to predict cervical cancer susceptibility in a north Indian population. However, such studies need to be carried out in different ethnic populations in order to discover the specific risk alleles, genotypes and combinations for disease prediction

Cyclooxygenase 1 [COX1] expression in type 2 diabetes mellitus: a preliminary study from north India

Background and purpose: The 6th edition of International Diabetes Federation, 2014 shows an estimate of 387 million people with Type 2 diabetes mellitus [T2DM] worldwide, expected to rise to 592 million by 2035. T2DM is a metabolic disorder, one of the reasons being oxidative stress due to impairment in antioxidant enzymes. It leads to several complications such as micro and macrovascular diseases. Cyclooxygenase1 [COX1] enzyme is the rate limiting factor for the arachidonic pathway leading to vascular wall contraction with angiotensin II occurring in heart diseases resulting from T2DM. COX1 determines 6-Keto Prostaglandin F1alpha [6-k-PGF1alpha] level, plays a major role in vasodilation and restricts macrophage platelet aggregation. The aim of the present study was to compare the COX1 expression and level of reactive oxygen species [ROS] in T2DM patients and controls at different time periods in human macrophages in order to find a biomarker or drug target

Subjects and methods: The study subjects consisted of 100 individuals, 50 each from T2DM patients and healthy sex/age matched controls. Cell proliferation by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assay and ROS measurement by 2',7'-dichlorofluorescein diacetate [DCFDA] staining were performed at different time periods [24, 48, 72 h]. COX1 mRNA expression was checked by relative quantification method after real-time polymerase chain reaction [RT-PCR]

Results: The MTT assay showed that cell viability was significantly higher at 48 h [P < 0.05]. ROS production was found to be lowest at 24 h by DCFDA staining. ROS levels were raised in T2DM patients as compared to controls. The quantitative RT-PCR analysis showed that the COX1 expression was higher in T2DM patients as compared to healthy controls although not significant [P > 0.05]

Conclusion: Although COX1 is known to be a "housekeeping" gene, our study showed that its expression can be correlated with the disease condition and be used as a marker. However, further studies are required in more number of samples from other ethnic populations to confirm the findings

Surveillance data on micro-organisms in respiratory tract infections at a tertiary care teaching hospital in South India.

Background: Respiratory tract infections are the leading cause of infections and associated hospitalizations in India. Generally, there is little control on the use of antibiotics. Community awareness of the issues involved in antibiotic therapy is poor and this is compounded by over-the-counter availability. The main aim was to compare the resistance developed by respiratory microbes. Methods: A retrospective and prospective study was designed and conducted to compare the pattern of resistance developed by microorganisms affecting the respiratory tract. Results: The sensitivity of K. pneumoniae to cefepime/tazobactum has decreased from 91.9% to 47.6% and S. aureus to Linezolid has decreased from 93.4% to 80% and S. pyogenes to azithromycin from 51.4% to 24.8%. Whereas sensitivity pattern of S. pneumoniae to amoxicillin/clavulanate is increased from 65.6% to 82.3%. The prevalence of Klebsiella pneumoniae was increased 19% to 25.2% whereas the prevalence of S. pneumoniae was decreased from 66.8% to 65.2%. Our study suggests that all microorganisms isolated are susceptible to carbapenems and cefepime/tazobactum in the cephalosporin class. Conclusions: There is major shift in the sensitivity pattern of microorganisms towards antibiotics. Therefore, these results must be kept in mind by the practitioners in the study site, prior to making decisions over a medication regimen empirically for patients and also to maximize the output of medications by rational prescribing and dosing.

Endothelial nitric oxide synthase (eNOS) VNTR as a probable marker in type 2 diabetes mellitus.

Background: The gene encoding eNOS is located on chromosome 7q36, a genetic region previously linked to metabolic syndrome, cardiovascular and renal diseases. Generally, in diabetes there are numerous genes involved, each being a small contributor in type 2 diabetes mellitus (T2DM) manifestation. A 27 bp variable number of tandem repeat (27 bp VNTR a/b) in intron 4 of enos gene has gained attention and this polymorphism may affect the expresssion of eNOS. We studied the association of eNOS-27 bp VNTR with T2DM in north indian population. Material and methods: Blood samples were collected in 0.5 M EDTA from 200 T2DM patients and 210 age/sex matched healthy controls. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) using the salting out method. The 27-VNTR polymorphism was determined by standard PCR amplification using forward and reverse primers 5'-AGGCCCTATGGTAGTGCCTTT-3’ and 5'-TCTCTTAGTGCTGTGGTCAC-3’ respectively. The genotypes were determined by analyzing the amplified products on 2% agarose gels. Genotypic and allelic frequencies were calculated by SPSS (version 15.0). Results: Clinical and biochemical profiles of healthy controls and T2DM cases as well as gender wise comparisons showed significant association in certain parameters (p<0.001). Five different alleles (I, II, IV, V and VI) were found in the study population. The genotypic frequency was significantly associated with T2DM (P <0.001). Conclusion: A significant role of allele ‘I’ in T2DM susceptibility was an interesting observation. Therefore, The 27 bp VNTR in eNOS gene polymorphism can be used as a probable marker in determining susceptibility to T2DM in north Indian population.

Interleukin-6 (IL-6)-597 A/G (rs1800797) & -174 G/C (rs1800795) gene polymorphisms in type 2 diabetes.

Background & objectives: Diabetes is a metabolic pro-inflammatory disorder characterized by chronic hyperglycaemia and increased levels of circulating cytokines suggesting a causal role for inflammation in its aetiology. In order to decipher the role of interleukin-6 (IL-6) in type 2 diabetes mellitus (T2DM) we analyzed two promoter polymorphisms -597 A/G (rs1800797) and -174 G/C (rs1800795) in T2DM cases from north India, and in healthy controls. methods: DNA was isolated from venous blood samples of T2DM patients (n=213) and normal healthy controls (n=145). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed after biochemical analysis. The genotypic and allelic frequency distributions were analyzed. Results: The clinical/biochemical parameters of T2DM cases when compared to controls showed a significant difference. No significant association was observed with -597A/G polymorphism while, -174 G/C showed a highly significant association (P<0.001). In haplotypic analysis, combination of -597G*/-174C* showed significant association (P=0.010). Interpretation & conclusions: Our data suggest that IL-6 gene polymorphisms play a prominent role in T2DM disease susceptibility in population from north India.

To evaluate stereoacuity in patients with acquired esotropia and to determine factors associated with favourable outcomes.

Aim: To evaluate stereoacuity in patients with acquired esotropia and determine the factors associated with favorable outcomes. Materials and Methods: A total of 68 subjects aged 6 years and above were included in the study. Thorough clinical evaluation including binocular status examination using the Bagolini‑striated glass test, The Netherland Organization (TNO), and Randot stereo test were done. The subjects were divided into two groups 1 and 2, based on the amount of deviation. Statistical analysis of the result was performed. Result: The duration of misalignment in the group with deviation less than or equal to 8 prism diopters (PD) was 1.49 ± 0.86 years, whereas in the group with deviation more than or equal to 10 PD was 4.64 ± 2.99 years (P = 0.000). Among the subjects in group 1, 89.5% achieved fusion and 52.6% had stereoacuity on both TNO and Randot, whereas in group 2 40% achieved fusion and 3.3% stereopsis on both TNO and Randot (one case with only coarse stereopsis). A subanalysis within group 1 revealed a statistically significant difference for the duration of misalignment (P = 0.02), but a marginal difference for the amount of deviation (P = 0.3). Conclusion: A horizontal deviation up to 8 PD was compatible with stereopsis. Also, the duration of constant misalignment affects the attainment of stereopsis despite successful realignment.

Establishing biological reference intervals for novel platelet parameters (immature platelet fraction, high immature platelet fraction, platelet distribution width, platelet large cell ratio, platelet-X, plateletcrit, and platelet distribution width) and their correlations among each other.

Aims: This study aims to establish biological reference interval for novel platelet parameters. Settings and Design: A total of 945 healthy individuals, age ranges from 18 to 64 years (881 males and 64 females) coming for voluntary blood donation from June to August 2012 (3 months) were enrolled after exclusion of rejection criteria. Materials and Methods: The samples were assayed by running in complete blood count + reticulocyte mode on the Sysmex XE-2100 hematology analyzer and the reference interval for the population was calculated using Clinical and Laboratory Standards Institute guidelines. Statistical analysis used: Tests were performed using SPSS (Statistical Product and Service Solutions , developed by IBM corporation), version 13. Student t test and pearsons correlation analysis were also used. Results: The normal range for various parameters was platelet count: 150-520 × 103/cu mm, immature platelet fraction (IPF): 0.3-8.7%, platelet distribution width (PDW): 8.3-25.0 fL, mean platelet volume (MPV): 8.6-15.5 fL, plateletcrit (PCT): 0.15-0.62%, high immature platelet fraction (H-IPF): 0.1-2.7%, platelet large cell ratio (P-LCR): 11.9-66.9% and platelet-X (PLT-X) (ch): 11.0-22.0. Negative correlation was observed between platelet count (r = −0.468 to r = −0.531; P < 0.001) and PCT (r = −0.080 to r = −0.235; P < 0.05 to P < 0.001) with IPF, PDW, MPV, H-IPF, P-LCR, and platelet-X. IPF/H-IPF showed a positive correlation among them and also with PDW, MPV, P-LCR, platelet-X (r = +0.662 to r = +0.925; P < 0.001). Conclusions: These novel platelet parameters offer newer avenues in research and clinical use. Establishing biological reference interval for different platelet parameters would help determine true high and low values and help guide treatment decisions.

Reactive metabolites and antioxidant gene polymorphisms in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM), by definition is a heterogeneous, multifactorial, polygenic syndrome which results from insulin receptor (IR) dysfunction. It is an outcome of oxidative stress caused by interactions of reactive metabolites (RMs) with lipids, proteins and other molecules of the human body. Production of RMs mainly superoxides (•O2 −) has been found in a variety of predominating cellular enzyme systems including nicotinamide adenine dinucleotide phosphate oxidase, xanthine oxidase, cyclooxygenase, endothelial nitric oxide synthase (eNOS) and myeloperoxidase. The four main RM related molecular mechanisms are: increased polyol pathway flux; increased advanced glycation end‑product formation; activation of protein kinase C isoforms and increased hexosamine pathway flux which have been implicated in glucose‑mediated vascular damage. Superoxide dismutase, catalase, glutathione peroxidase, glutathione‑S‑transferase and NOS are antioxidant enzymes involved in scavenging RMs in normal individuals. Functional polymorphisms of these antioxidant enzymes have been reported to be involved in the pathogenesis of T2DM. The low levels of antioxidant enzymes or their non‑functionality results in excessive RMs which initiates stress related pathways thereby leading to IR and T2DM. An attempt has been made to review the role of RMs and antioxidant enzymes in oxidative stress resulting in T2DM.

Development of natural gum based glipizide mucoadhesive microsphere.

The objective of this study was to develop glipizide microsphere with natural gums. Guar gum and xanthan gum were used separately in different ratios as natural polymers. The microspheres were prepared by orifice ionic gelation method and they were characterized by scanning electron microscopy and particle size analysis. Among six formulations, microspheres of four formulations (F1-F4) were discrete, sphrerical and free flowing. There was an inverse relationship found between the amount of gum and surface smoothness in case of guar gum-containing microspheres while a forward relationship was found between amount of gum and surface smoothness in case of the microspheres containing xanthan gum. The size of the particles increased with increasing amounts of gum. It can be concluded that guar gum and natural gum at a ratio of 1:0.25 and 1:0.5 can be ideal for formulating natural gum based glipizide mucoadhesive microsphere.

APE1/Ref-1 as an emerging therapeutic target for various human diseases: phytochemical modulation of its functions

Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme involved in the base excision repair (BER) pathway, which repairs oxidative base damage caused by endogenous and exogenous agents. APE1 acts as a reductive activator of many transcription factors (TFs) and has also been named redox effector factor 1, Ref-1. For example, APE1 activates activator protein-1, nuclear factor kappa B, hypoxia-inducible factor 1alpha, paired box gene 8, signal transducer activator of transcription 3 and p53, which are involved in apoptosis, inflammation, angiogenesis and survival pathways. APE1/Ref-1 maintains cellular homeostasis (redox) via the activation of TFs that regulate various physiological processes and that crosstalk with redox balancing agents (for example, thioredoxin, catalase and superoxide dismutase) by controlling levels of reactive oxygen and nitrogen species. The efficiency of APE1/Ref-1's function(s) depends on pairwise interaction with participant protein(s), the functions regulated by APE1/Ref-1 include the BER pathway, TFs, energy metabolism, cytoskeletal elements and stress-dependent responses. Thus, APE1/Ref-1 acts as a 'hub-protein' that controls pathways that are important for cell survival. In this review, we will discuss APE1/Ref-1's versatile nature in various human etiologies, including neurodegeneration, cancer, cardiovascular and other diseases that have been linked with alterations in the expression, subcellular localization and activities of APE/Ref-1. APE1/Ref-1 can be targeted for therapeutic intervention using natural plant products that modulate the expression and functions of APE1/Ref-1. In addition, studies focusing on translational applications based on APE1/Ref-1-mediated therapeutic interventions are discussed.