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Background: Micro-ribonucleic acids (miRNAs) are small non-coding RNAs that regulate gene expression. Expression of miRNAs has been shown to be dysregulated in patients with breast cancer. These markers have been shown to be potential markers of diagnostic significance. We intended to study the usefulness of miRNA-155 and miRNA-205 in monitoring response to surgery by monitoring their pre- and post-operative expression. Methods: Twenty patients newly diagnosed with malignant breast disease along with 20 age-matched females not having any breast lesion were included in the study. Reverse transcription-polymerase chain reaction was used to assess the expression of circulating miRNAs. Results: MiRNA-155 was found to be significantly upregulated and miRNA-205 was significantly downregulated in patients with breast cancer compared to controls. There was no change in expression of miRNA-155 and miRNA-205 following surgery. Conclusions: The findings of the present study do not support the role of miRNA-155 and miRNA-205 as markers suitable for follow-up. However, the findings of the present study need to be confirmed in a larger sample size and samples collected over a defined post-operative period. [ABSTRACT FROM AUTHOR]

Background: Compared to the developed world, the pattern of acute kidney injury (AKI) is different in tropics. The present study was undertaken to study the epidemiological profile and outcomes in AKI. Methods: This prospective observational study was conducted in a tertiary care teaching hospital in South India. Demographic details, detailed medical history, aetiological factors, comorbid conditions, prognostic factors and outcomes were studied. Acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were calculated at admission for every patient to know the prognosis. Results: A total of 193 patients who fulfilled the inclusion criteria were enrolled in the study. Majority of the patients were in their sixth decade of life. The mean age was 52.1 ± 14.8 years (male:female = 1.7:1). Hypertension (41.5%; n = 80) and diabetes mellitus (33.7%; n = 65) were the most common comorbid illnesses in our patients. The average duration of hospital stay was 8 days. AKI was secondary to medical causes in 69.4% (134/193), surgical causes in 25.4% (49/193) and obstetric is 5.18% (10/193). Renal replacement therapy was required in 56.4% (n = 109) of the study population. The mortality rate observed in our study was 21.8% (n = 42). The mean APACHE II score and mean SOFA score were found to be significantly higher in the non survivors compared to the survivors. Conclusions: Patients with AKI who have higher APACHE II or SOFA score should be carefully monitored and aggressively treated to reduce mortality. [ABSTRACT FROM AUTHOR]

Background and Objective: Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis of common occurrence. Adiponectin is an adipocytokine shown to exert anti‑inflammatory as well as pro‑inflammatory effects. Our objective was to study the serum adiponectin levels in RA and explore its association with RA disease activity. Materials and Methods: Forty RA patients (newly diagnosed n = 20, RA in clinical remission n = 20) and thirty age‑, gender‑, and body mass index (BMI)‑matched apparently healthy controls were included. Serum adiponectin levels were measured by enzyme‑linked immunosorbent assay. RA clinical remission was defined by a Disease Activity Score 28 of <2.6. Results: Serum adiponectin levels were significantly lower in RA patients compared to controls. Both groups of RA patients had lower adiponectin levels than controls. There was no difference in adiponectin levels between the two groups of RA patients. There was no association of adiponectin with disease activity or BMI. Conclusions: Serum adiponectin concentration is decreased in RA patients and was not associated with disease activity. [ABSTRACT FROM AUTHOR]

Background: Prostate Specific Antigen (PSA) is secreted by prostate gland as well as hormonally regulated tissues such as breast, ovaries and endometrium. We aimed to assess the utility of serum total and free PSA in combination with carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA 15-3) in diagnosis of breast cancer. Methods: Seventy two female patients (38 with benign breast disease and 34 with malignant breast disease) who were histologically, cytologically confirmed with diagnosis of primary breast tumours were investigated. Serum total prostate specific antigen (PSA), Free PSA, CEA, CA 15-3 were analysed by enzyme linked immunosorbent assay (ELISA) method. Diagnostic performance of markers was studied using receiver operating characteristic curve and logistic regression analysis. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results: Patients with malignant breast cancer had significantly higher levels of all tumour markers compared to benign breast tumours. A significant decrease in total PSA, CEA and a statistically insignificant decrease in free PSA concentrations were seen in malignant breast cancer patients after surgery. Performance of total PSA was best among all the markers with 100% sensitivity, NPV, 94.7% specificity and 94.4% PPV. Conclusions: Serum total PSA is a good diagnostic marker to differentiate benign breast disease from malignant tumours compared to currently used CEA and CA 15-3. [ABSTRACT FROM AUTHOR]

The pleiotropic cytokine osteopontin (OPN) is found to be involved in the pathogenesis of both kidney and cardiovascular disease (CVD). We evaluated the relationship between OPN, other cardiovascular risk factors and carotid intima-media thickness (CIMT) in chronic kidney disease (CKD) (predialysis) patients. This is a 2-year cross-sectional prospective study involving 75 patients with CKD from stage 1 to stage 5 attending the nephrology outpatient department and 25 healthy controls. Routine biochemical parameters were analyzed on clinical chemistry Autoanalyzer Beckman Coulter DXC 600 Synchron, USA. OPN was estimated by ELISA method. Carotid intima-media wall thickness was estimated by Doppler of carotid vessels. Serum OPN and other nontraditional cardiovascular risk factors such as CIMT, lipoprotein (a) Lp(a), fibrinogen, and homocysteine were significantly increased in patients of CKD compared to controls. OPN, Lp(a), fibrinogen, CIMT, parathyroid hormone, and homocysteine progressively increased from early stages of CKD and increased further with progression of the disease, but nitric oxide (NO) level progressively decreased with progression of CKD. OPN showed a positive correlation with CIMT, Lp(a), fibrinogen, and homocysteine and negative correlation with estimated glomerular filtration rate and NO. There was a close direct association between circulating levels of OPN and the presence of atherosclerotic plaques in carotid arteries of patients with CKD. Osteopontin and nontraditional CVD risk factors are altered in early stages of CKD and might predict adverse outcomes in these patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Arginine, citrulline and asymmetric dimethylarginine (ADMA) are three molecules in the nitric oxide (NO) pathway which provide useful information about vascular endothelial function. ADMA accumulates with patients with chronic kidney disease (CKD) and inhibits NO synthesis. We describe the modification of a previously established method for the measurement of amino acids analysis for simultaneous detection of arginine, citrulline, and ADMA in plasma and to validate its performance in patients with CKD. MATERIALS AND METHODS: Arginine, citrulline, and ADMA were simultaneously separated by reverse-phase high-performance liquid chromatography by precolumn derivatization with O-phthalaldehyde using the modified method. It was then applied for analysis in thirty patients with CKD and thirty healthy controls so as to cover the entire measuring range, i.e., normal and uremic range. RESULTS: The method showed a good performance in terms of linearity, precision, and recovery. The detection limit of the assay for ADMA was found to be 0.05 μmol/L at a signal-to-noise ratio of 3:1. The average within run coefficient of variation for ADMA using this method was 4.7% in the normal range and 1.9% in the uremic range, while the average between-day precision in the normal and uremic range was 6.5% and 5.2%, respectively. Patients with CKD were found to have higher concentration of ADMA compared to controls. CONCLUSION: This method can be useful in assessing the baseline cardiovascular risk in an individual as well as in the follow-up of the patients who are receiving L-arginine, and thus, assess the response to treatment by simultaneous measurement of arginine and ADMA. [ABSTRACT FROM AUTHOR]

Several cardiovascular disease (CVD) risk factors have been identified among patients with chronic kidney disease (CKD). Gut-derived uremic toxins (GDUT) are important modifiable contributors in this respect. There are very few Indian studies on GDUT changes in CKD. One hundred and twenty patients older than 18 years diagnosed with CKD were enrolled along with forty healthy subjects. The patients were classified into three groups of forty patients based on stage of CKD. Indoxyl sulfate (IS), para cresyl sulfate (p-CS), indole acetic acid (IAA), and phenol were estimated along with the assessment of oxidative stress (OS), inflammatory state, and bone mineral disturbance. All the GDUT increased across the three groups of CKD. All patients had higher levels of malondialdehyde (MDA), ferric reducing ability of plasma (FRAP), high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6) as compared to controls. IS and IAA showed positive association with MDA/FRAP corrected for uric acid, whereas IS and p-CS showed positive association with IL-6. IS, IAA, and phenol showed a positive association with calcium x phosphorus product. GDUT increase OS and inflammatory state in CKD and may contribute to CVD risk. [ABSTRACT FROM AUTHOR]

Dacryolith are concretions observed in any part of nasolacrimal system, but stones within the lacrimal ductules are rare. Dacryolith are usually comprised of organic material, proteins and mucoproteins with approximately 20% amino acid content, epithelial cells and other debris. The clinical presentation and chemical composition of the dacryolith are variable. We report the case of lacrimal ductular dacryolith in a 10-year-old girl who presented with complaints of discharge of hard stone like material from the left eye. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) analysis were carried out to find the chemical composition of the stone. The results showed 65 kDa protein indicating the presence of albumin and high amount of calcium carbonate in the stone substantiating the presence of albumin in lacrimal sac. [ABSTRACT FROM AUTHOR]

Background: Thyroid dysfunction can have a negative impact on cognitive functions in young girls in adolescent age group as well as affect their future development of infertility, reproductive dysfunction and poor pregnancy outcome. Methods: Cross-sectional study of burden of thyroid disorders in 70 medical undergraduate students of 17-19 years age group studying in Sri Venkateswara Institute of Medical Sciences, Sri Padmavathi Medical College for Women, Tirupati. Results: Among the 70 female subjects screened for thyroid disorders, a single subject was found to have subclinical hypothyroidism. The thyroid stimulating hormone (TSH) level of this subject was 8.1 mIU/L, which is considered to be mildly elevated from the normal range and the thyroxine levels were 89 ng/mL which is within the normal reference range. Her anti-TPO antibodies test results were negative. Conclusions: Identification of subclinical hypothyroidism in asymptomatic young girls in adolescent age group can help in initiating treatment early. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular (CVD) morbidity and mortality, mainly due to atherosclerosis. Decreased production or reduced bioavailability of nitric oxide (NO) can result in endothelial dysfunction (ED). Multiple mechanisms are known to cause a state of NO deficiency in patients with CKD. Patients in various stages of CKD grouped as group-1 (CKD stage 1 and 2), group-2 (CKD stage 3 and 4), group-3 (CKD stage 5) and healthy controls were included in the study. Each group of patients and controls comprised 25 subjects. Plasma nitrites, L-arginine, asymmetric dimethyl arginine (ADMA) and citrulline were measured in all the subjects. Patients in all stages of CKD had lower NO and higher ADMA levels compared to controls. Further, group-2 and group-3 patients had lower levels of NO and higher levels of ADMA than group-1 patients. L-arginine levels showed no difference between patients and controls. However, group-3 patients had lower L-arginine levels compared to group-1 patients. Citrulline levels were decreased in group-3 patients. NO production was decreased in patients in all stages of CKD. The decrease could be due to decreased availability of the substrate, L-arginine or due to an increased ADMA, a potent inhibitor of endothelial NO synthase. Therapeutic interventions directed towards improvement of NO production in addition to management of other CVD risk factors may prevent development of ED and facilitate proper management of CKD patients who are at increased risk for CVD. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. The increased prevalence of obesity, diabetes, hypertension, hypertriglyceridaemia and hypercholesterolemia are considered to be the potential causative factors for NAFLD. NAFLD is emerging as a major clinical problem worldwide. Recently much attention has been focused in India as the prevalence of obesity and diabetes is rising. NAFLD is responsible for unexplained raise in transaminases, and an important cause of cryptogenic cirrhosis and cryptogenic hepatocellular carcinoma in India. NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), potentially leading to fibrosis and cirrhosis. Studies have suggested that the adipokines are involved in the pathogenesis of NAFLD and its progression to NASH, through their metabolic and pro- or anti-inflammatory activity. Adipokines in particular tumor necrosis factor-α and interleukin-6 are believed to mediate the shift in pathology from steatosis to steatohepatitis. In addition, other adipokines such as adiponectin, leptin and resistin also play a crucial role in the development and progression of NAFLD through their metabolic and pro-or anti-inflammatory activity. This suggests that imbalance between pro-inflammatory and anti-inflammatory cytokines may have a role in the development of liver damage in NAFLD. Understanding the relationship between adipokines and NAFLD may play an important role in the early identification/diagnosis, treatment and also help in preventing disease progression. [ABSTRACT FROM AUTHOR]

Oxidative stress as a result of disequilibrium between free radical generation and antioxidant status has been implicated in several pathologies including thyroid diseases. Studies on antioxidant status in overt (OHT) and subclinical hypothyroidism (SHT) are controversial and limited. The aim of this study was to determine the effect of OHT and SHT on antioxidant status. Thirty-six patients with OHT, 36 patients with SHT, and 39 healthy euthyroid subjects as the control group were included in the study. Plasma levels of malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (TAC) as ferric reducing ability of plasma (FRAP), and erythrocyte antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), SOD/GPx ratios, catalase (CAT), and glutathione reductase (GR) were analyzed in all groups. MDA and GPx values were elevated, while GSH, FRAP, SOD, and SOD/GPx ratio were decreased in both patient groups compared with controls. No change in activities of CAT and GR were observed in both the patient groups. Significant differences were observed between OHT and SHT groups with high MDA, GPX and low GSH, FRAP, SOD, and SOD/GPx ratio in OHT group. Thus, hypothyroid patients have a deficient antioxidant defense in the form of decreased activity of SOD, decreased levels of FRAP and GSH along with an increase in GPx activity. The severity of the disease appears to decide the degree of deficiency and our findings also point to this, in the form of decrease in SOD, FRAP, and GSH observed being more in OHT than in SHT patients. Hormonal changes and increased lipid peroxidation, which also vary with severity of disease, appear to contribute to the antioxidant deficiency. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted to compare serum lipoprotein (a) and homocysteine levels in newly diagnosed patients with hypothyroidism and normal control subjects. It is noted that the study of 25 newly diagnosed patients with hypothyroidism revealed that lipoprotein (a) and homocysteine may increase risk of cardiovascular disease (CVD) in hypothyroid patients.

In the normal circumstances the proliferation of body cells is under strict control. The cells differentiate, divide and die on a sequential manner in a healthy organism. Cancer is characterized by loss of control of cellular growth and development leading to excessive proliferation and spread of cells. Cancer derived from a Latin word meaning crab. It is presumed that the word cancer originated from the character of cancerous cells which can migrate and adhere and cause pain (like a crab) to any part of the body. [ABSTRACT FROM AUTHOR]

Accelerated atherosclerosis and cardiovascular disease are major causes of morbidity and mortality in patients of end-stage renal disease. Carotid intima media thickness is taken as a useful surrogate marker of atherosclerosis. Thirty end-stage renal disease (ESRD) patients were subjected to ultrasonography to study CIMT before the initiation of dialysis. CIMT was found to be higher in ESRD patients than in controls. Levels of a serum marker of oxidative stress were also found to be higher in patients than in the controls. CIMT is an easy, noninvasive, reproducible, and cost-effective investigation in patients with chronic renal failure. [ABSTRACT FROM AUTHOR]

Introduction: Postmenopausal women constitute an ideal model for studying the extent of hypothalamo-pituitary-gonadal (HPG) axis suppression in critical illness as the gonadotropinsare normally high and non-cyclical in them. Objectives: The objective of this study is (i) to assess the impact of acute severe illness on the HPG axis in postmenopausal women, (ii) to correlate the severity of illness with (a) activity of the HPG axis, (b) the activity of the hypothalamo-pituitary-adrenal axis, (c) activity of the hypothalamo-pituitary-thyroid axis and (d) serum prolactin. Methods: A total of 35 postmenopausal women older than 60 years admitted to medical intensive care with a simplified acute physiology score II (SAPS II) more than 30, consistent with a predicted in-hospital mortality of greater than 10% were recruited. On day 5 of their hospital stay, blood samples were collected for estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol, androstenedione and prolactin and thyroid profile. As controls, 35 apparently healthy postmenopausal women were recruited. Results: Levels of LH, FSH, free thyroxin (fT4) and triiodothyronine were lower while estradiol, cortisol and androstenedione were higher among patients in comparison with healthy controls. Prolactin levels were similar in patients and controls. Among sick patients both FSH and fT4 showed a negative correlation (P < 0.05) with the SAPS II score. Conclusions: Estrogens are paradoxically elevated despite gonadotropin suppression in critically ill postmenopausal women, suggesting a non-ovarian origin of the same. Prolactin remained unaltered despite illness in patients, possibly reflecting atrophy of lactotrophs in menopause. [ABSTRACT FROM AUTHOR]

Background & Objectives: Glycosylated haemoglobin (HbA1c) has been in use for more than a decade, as a diagnostic test for type 2 diabetes. Validity of HbA1c needs to be established in the ethnic population in which it is intended to be used. The objective of this study was to derive and validate a HbA1c cut-off value for the diagnosis of type 2 diabetes in the ethnic population of Rayalaseema area of south India. Methods: In this cross-sectional study, consecutive patients suspected to have type 2 diabetes underwent fasting plasma glucose (FPG) and 2 h post-load plasma glucose (2 h-PG) measurements after a 75 g glucose load and HbA1c estimation. They were classified as having diabetes as per the American Diabetes Association criteria [(FPG ≥7 mmol/l (≥126 mg/dl) and/or 2 h-PG ≥11.1 mmol/l (≥200 mg/dl)]. In the training data set (n = 342), optimum cut-off value of HbA1c for defining type 2 diabetes was derived by receiver-operator characteristic (ROC) curve method using oral glucose tolerance test results as gold standard. This cut-off was validated in a validation data set (n = 341). Results: On applying HbA1c cut-off value of >6.3 per cent (45 mmol/mol) to the training data set,sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing type 2 diabetes were calculated to be 90.6, 85.2, 80.8 and 93.0 per cent, respectively. When the same cut-off value was applied to the validation data set, sensitivity, specificity, PPV and NPV were 88.8 , 81.9, 74.0 and 92.7 per cent, respectively, although the latter were consistently smaller than the proportions for the training data set, the differences being not significant. Interpretation & conclusions: HbA1c >6.3 per cent (45 mmol/mol) appears to be the optimal cut-off value for the diagnosis of type 2 diabetes applicable to the ethnic population of Rayalaseema area of Andhra Pradesh state in south India. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is one of the most important noncommunicable diseases. Abnormal concentration of some tumor markers were found in a spectrum of nonmalignant diseases such as benign ovarian tumors, breast diseases, chronic hepatitis, cirrhosis, diseases of the bile duct, and in CKD. Hence, the present study was undertaken to evaluate carbohydrate antigen (CA) 15-3, carcinoembryonic antigen (CEA), CA 19-9, and human chorionic gonadotropin (HCG) concentrations in advanced stages of CKD (Stage 4 and 5) patients who are not on dialysis and with no known malignancy. Patients included 40 CKD patients and 40 healthy controls. CA 15-3, CEA, CA 19-9, and HCG in serum were estimated by enzyme-linked immunosorbent assay method. The differences in tumor marker levels between the controls and advanced stages of CKD (Stage 4 and 5) were assessed using one-way analysis of variance using the Statistical Package for the Social Sciences for Windows version 16.5. CKD patients had significantly elevated levels of CEA, HCG, CA 19-9, and CA 15-3 compared to the control group (P = 0.001). There was no difference in the tumor markers levels between CKD Stage 4 and 5. Elevation in serum tumor markers may be a possibility in patients with CKD even in the situations of the absence of a malignancy. This may be due to an alteration in their metabolism in CKD and reduction of glomerular filtration rate leading to impaired excretion. Hence, it may be prudent to exercise caution in the interpretation of serum tumor markers as a representative for underlined malignancy in patients of CKD., Competing Interests: None

Administration of iodinated contrast media is associated with serious complications such as acute kidney injury (AKI). Oxidative stress is implicated as a major mechanism underlying the production of contrast-induced AKI (CI-AKI). There are very few human studies on oxidative stress occurring after contrast administration. Twenty-seven patients scheduled for coronary angiography were recruited. An average of 22.2 mL low-osmolal nonionic contrast was administered. Plasma conjugated dienes (CD), lipid hydroperoxides (LOOH), malondialdehyde (MDA), protein carbonyl (PC), protein thiols (PTs), ferric reducing ability of plasma (FRAP), erythrocyte super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase were estimated before, 30 min, 2 and 4 h after contrast administration. CD, LOOH, MDA, and PC increased (P <0.001), whereas PTs, FRAP, SOD, CAT (P <0.001), and GPx (P = 0.013) decreased in the first 4 h. Estimated glomerular filtration rate (eGFR) showed inverse association with MDA and positive association with GPx. The study provides evidence for oxidative stress following contrast administration even in the absence of predisposing factors. Association of eGFR with MDA and GPx indicate kidney as the source of oxidative stress. Hence, antioxidant therapy before contrast administration helps to prevent the development of oxidative stress, thereby reducing the risk of CI-AKI.

Accelerated atherosclerosis and cardiovascular disease are major causes of morbidity and mortality in patients of end-stage renal disease. Carotid intima media thickness is taken as a useful surrogate marker of atherosclerosis. Thirty end-stage renal disease (ESRD) patients were subjected to ultrasonography to study CIMT before the initiation of dialysis. CIMT was found to be higher in ESRD patients than in controls. Levels of a serum marker of oxidative stress were also found to be higher in patients than in the controls. CIMT is an easy, noninvasive, reproducible, and cost-effective investigation in patients with chronic renal failure.

Background and Aim: Higher prevalence of coronary heart disease (CHD) has been reported in south Indian population, which cannot be accounted for by the traditional risk factors like hyperlipidemia. Identification of new risk factors may help in treatment and prevention of CHD in this part of the world. In an attempt to investigate the causes of increased incidence of CHD in this part of the world, we intended to look for oxidative stress in our patients as a possible risk factor. As an initial step in this perspective, a case- control study was conducted to find out the serum antioxidant levels and their association with CHD in south Indian population., Settings and Design: A tertiary care hospital; Case--control study., Materials and Methods: One hundred thirty nine angiographically proven CHD patients (aged 29-75 years) were studied against 59 population based healthy controls (aged 29-72 years) free of CHD. Fasting serum cholesterol, triglycerides, HDL cholesterol, erythrocyte and plasma glutathione peroxidase and superoxide dismutase were estimated on automated clinical chemistry analyzer. LDL cholesterol and VLDL cholesterol were calculated. Vitamins A and E were estimated using high performance liquid chromatography (HPLC)., Statistical Analysis: Unpaired t test was used to compare means. Binary logistic regression was done to find out the association between dependent and independent variables., Results: Significantly higher levels of Total Cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratio and lower HDL cholesterol levels were observed in patients when compared to controls. No significant difference of plasma and erythrocyte glutathione peroxidase and superoxide dismutase activity was observed between patients and controls. Significantly lower levels of vitamin E in patients than in controls was observed (P<0.001). Serum vitamin E was inversely associated with coronary heart disease even after controlling for age and other coronary risk factors (Odds ratio 0.898, 95% CI 0.826-0.976 P=0.01)., Conclusions: The results of present study suggest that deficiency of vitamin E may be an independent risk factor of CHD. This study brings out the need for long- term monitoring of vitamin E supplementation as a preventive measure for CHD in the population studied.