Hepatocyte Growth Factor in Predialysis and Hemodialysis Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) which is characterized by progressive loss of renal function and renal fibrosis is a worldwide public health problem. Hepatocyte growth factor (HGF) is a polypeptide that exhibits multiple functions including antifibrotic effects on kidneys. The present study was aimed at evaluating HGF levels and studying its association with markers of inflammation and oxidative stress in patients of predialysis and dialysis CKD. A total of 80 subjects including 20 healthy controls, 40 patients of CKD stage 1 to stage 5 (predialysis), and 20 CKD patients with end-stage renal disease on hemodialysis were recruited. HGF, high-sensitivity C-reactive protein (hsCRP), malondialdehyde (MDA), and ferric reducing ability of plasma (FRAP) were measured in all the subjects. HGF levels were significantly higher in all patients with CKD compared to controls. The levels were found to be lower in patients on dialysis than in the predialysis group; however, the difference was not statistically significant. hsCRP, MDA, and FRAP were significantly higher in all patients with CKD than in controls. HGF levels did not show a significant correlation with the markers studied. HGF levels were increased in response to renal injury in CKD patients. The levels were higher in predialysis patients of CKD than in CKD patients on dialysis. HGF levels may be used as an indicator of renal fibrosis in patients with CKD.

Efficacy of oral rosuvastatin intervention on HDL and its associated proteins in men with type 2 diabetes mellitus.

PURPOSE: High-density lipoprotein (HDL) undergoes structural and functional modification in patients with type 2 diabetes mellitus (T2DM). There are limited data on effect of rosuvastatin on HDL-associated proteins and the antiatherogenic effects of rosuvastatin. The present study intended to study the efficacy of rosuvastatin intervention on HDL-associated proteins and its other antiatherogenic effects in men with T2DM. METHODS: Men with T2DM on oral antidiabetic treatment, with LDL-C levels > 75 mg/dL and willing for rosuvastatin intervention (20 mg/day orally for a period of 12 weeks), were included. Fasting glucose, lipid profile were measured using standard methods. Oxidized low-density lipoprotein (oxLDL), oxidized HDL (oxHDL), paraoxonase-1 (PON-1), tumour necrosis factor-α (TNF-α) and lecithin:cholesterol acyltransferase (LCAT) in serum were measured by ELISA; serum myeloperoxidase (MPO) by spectrophotometric method and cholesterol efflux by fluorometric assay. Carotid intima-media thickness (cIMT) measurement to assess vascular health status was done using doppler. RESULTS: Rosuvastatin produced a significant decrease (p < 0.05) in lipids (total cholesterol, triglycerides, LDL-C); oxidative stress (oxLDL, oxHDL, MPO); inflammation (TNF-α); LCAT concentration; cIMT; significant increase in antiatherogenic HDL and cholesterol efflux (p < 0.05) and no change in apoA-I levels from baseline to 12 weeks of follow-up. A decrease in MPO activity was found to be independently associated with an increase in cholesterol efflux. CONCLUSIONS: Post intervention there is a quantitative and qualitative improvement in HDL, which helps in its reverse cholesterol transport (RCT) and antioxidant functions. Improvement in HDL functions and suppression of inflammation by rosuvastatin lead to regression in cIMT, which is beneficial in decreasing the progression of cardiovascular disease (CVD) in men with diabetes.

Correction to: Efficacy of oral rosuvastatin intervention on HDL and its associated proteins in men with type 2 diabetes mellitus.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Plasma osteopontin levels in patients with acute kidney injury requiring dialysis: a study in a tertiary care institute in South India.

PURPOSE: Osteopontin (OPN) is evolving as a novel biomarker of injury, overall survival and renal outcome in critically ill patients with acute kidney injury (AKI), requiring renal replacement therapy. METHODS: We performed a prospective study on 35 consecutive patients of acute kidney injury requiring renal replacement therapy (AKIN stage 3). OPN levels were measured in the patients and in the controls. The relation between OPN and the severity of illness and its effect on the AKI and renal outcome were studied. RESULTS: There was a statistically significant elevation of OPN in patients of AKIN stage 3 in comparison to healthy controls (p = 0.001). The Sequential Organ Function Assessment (SOFA) scores were found to be higher in septic group in comparison to non-septic group and it was statistically significant (p = 0.014). There was significant correlation between SOFA scoring and OPN levels suggesting its association with severity (r = 0.382, p = 0.023). CONCLUSIONS: In our study, OPN was found to be a valuable marker of severity of injury, its association with sepsis and renal recovery, in patients with acute kidney injury needing renal replacement therapy.

Serum tumor markers in advanced stages of chronic kidney diseases.

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.

Study of contrast-induced oxidative stress in nondiabetic patients undergoing coronary angiography.

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.

Osteopontin, Cardiovascular Risk Factors and Carotid Intima-Media Thickness in Chronic Kidney Disease.

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.

Changes in the inflammatory and oxidative stress markers during a single hemodialysis session in patients with chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) is a common cause of morbidity and mortality in end-stage renal disease (ESRD) patients on hemodialysis (HD) among whom it is 5-20 times higher than in the general population. Some of the nontraditional risk factors such as oxidative stress and inflammation are related to the progress of CVD in HD patients. Several, but not all studies, reported that inflammatory and oxidative stress markers are increased during a single session of HD, mimicking changes that occur during acute immune activation. This study was taken up to evaluate the changes in the inflammatory and oxidative stress markers during a single HD session in patients with chronic kidney disease. METHODS: Twenty-five ESRD patients on maintenance HD and 25 controls were included in the study. Blood samples were obtained from the patients before starting of hemodialysis (pre-HD) and after completion of hemodialysis (post-HD). The changes in serum Pentraxin-3, hs-CRP, malondialdehyde (MDA) and ferric reducing ability of plasma (FRAP) levels were measured in pre- and post-HD ESRD patients and compared with healthy control group. RESULTS: This study found increased levels of Pentraxin-3, hs-CRP, MDA, and decreased level of FRAP in HD patients compared to controls. CONCLUSIONS: Hemodialysis procedure contributes to inflammation and oxidative stress.

Carbamylated Hemoglobin can Differentiate Acute Kidney Injury from Chronic Kidney Disease.

Carbamylated hemoglobin (CarHb) was found to have a potential role in the differentiation of patients with acute kidney injury (AKI) from chronic kidney disease (CKD). This study was aimed at the evaluation of the diagnostic performance and usefulness of CarHb in the differentiation of AKI from CKD. Forty patients with renal disease and twenty age- and sex-matched healthy controls were included in the study. Urea, creatinine, Hb, and CarHb were measured in all the subjects. Patients with AKI and CKD were found to have significantly increased levels of CarHb when compared to controls (P < 0.05 for both groups). Patients with CKD had significantly increased levels of CarHb when compared to patients with AKI (P < 0.05). CarHb showed significant positive correlation with urea in patients with renal disease (r = 0.776, P < 0.0001). Significant area under curve (AUC = 0.840, P < 0.0001) was obtained for CarHb and a cut-off value of 98.33 µg VH/g Hb resulted with the best combination of 85% sensitivity and 75% specificity. CarHb may provide clinical utility since patients with AKI and CKD have similar clinical presentation usually. A cut-off value of 98.33 µg VH/g Hb has been found to be useful to differentiate AKI from CKDs.

Comparative safety evaluation of riot control agents of synthetic and natural origin.

Riot control agents (RCA) are lachrymatory, irritating compounds which temporarily incapacitate the uncontainable crowd. Ortho-Chlorobenzylidene-malononitrile (CS), 2-chloroacetophenone (CN), dibenz[b,f]1:4-oxazepine (CR), and nonivamide (PAVA) are synthetic RCAs, while oleoresin extract of chili known as oleoresin capsicum (OC) a natural irritant has been in use by various law enforcement agencies. Though efficacy of these agents is beyond doubt, they suffer from certain drawbacks including toxicity, production cost, and ecological compatibility. Presently, we have evaluated the safety of CR, OC, and PAVA on inhalation variables along with oral lethality. Additionally, the liver function test (LFT) in serum and lungs function was evaluated in broncho-alveolar-lavage fluid (BALF), both collected on the 14th day after RCA exposure. Animals then sacrificed and histopathology of liver and lungs was carried out. Results showed OC and PAVA to be more toxic than CR with an oral LD50 of 150 and 200 mg/kg body weight, respectively, while CR was safe at >3 g/kg body weight. All three agents caused severe impairment of respiratory variables bringing down normal respiration by >80% with rise in sensory irritation. Recovery from the irritating effect of CR was more rapid than OC and PAVA. LFT and BALF variables were not significantly different from that of control. There were no remarkable histopathological changes in liver and lungs. Hence, as per results, CR is safest among all synthetic and natural origin RCAs and can be safely used for effective dispersion of disobedient mob.

Impact of Severity of Illness on the Function of the Hypothalamo-pituitary-gonadal Axis in Postmenopausal Women with Acute Severe Illness: Implications for Predicting Disease Outcome.

BACKGROUND: While elevated levels of estradiol were predictive of mortality in critically ill surgical and trauma patients, their ability to predict outcome in nonsurgical patients has not been studied. We aimed to study the determinants of gonadotropin levels in acutely ill postmenopausal women with nonsurgical disease and the impact of changes in the gonadal axis on the outcome of these patients. METHODS: Thirty-five postmenopausal women admitted to medical intensive care with acute severe illness and having a Simplified Acute Physiology Score (SAPS II score) ≥30 (in-hospital mortality rate ≥ 10%) were recruited. On the 5th day of hospitalization, fasting samples were collected at 8.00 am and tested for luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, free triiodothyronine, free thyroxine, thyrotropin, cortisol, prolactin, dehydroepiandrosterone, androstenedione, and sex hormone-binding globulin. Multiple linear regression analysis was performed to identify independent determinants if any of LH and FSH. Receiver operating characteristic (ROC) curves were drawn for different cutoffs of LH, FSH, and estradiol to diagnose mortality and prolonged hospitalization. RESULTS: There was an independent negative association between the FSH and the SAPS II score (beta = -0.435; P = 0.014), but not with any of the other tested parameters (estradiol, prolactin, or cortisol). Among components of the SAPS II score, the total leukocyte count (TLC) was negatively associated with serum FSH (beta coefficient = -0.635, P = 0.013). None of these parameters were determinants of LH. On ROC analysis, neither estradiol nor gonadotropins were diagnostic for in-hospital mortality. However, among survivors, low estradiol was diagnostic for prolonged hospital stay (area under the curve = 0.785; P = 0.015). CONCLUSION: FSH, but not LH, is negatively associated with the severity of illness, particularly to its inflammatory component (TLC). Low estradiol in survivors was a predictor of prolonged hospital stay.

Simultaneous determination of arginine, citrulline, and asymmetric dimethylarginine in plasma by reverse-phase high-performance liquid chromatography.

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.

Role of Gut-derived Uremic Toxins on Oxidative Stress and Inflammation in Patients with Chronic Kidney Disease.

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 × phosphorus product. GDUT increase OS and inflammatory state in CKD and may contribute to CVD risk.

Biomarker response to contrast administration in diabetic and nondiabetic patients following coronary angiography.

Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C represent early renal injury markers for contrast-induced nephropathy (CIN). Baseline parameters such as type and quantity of contrast, patient preparation, renal function status, and diabetes mellitus (DM) are known to affect the response of the kidney to contrast-induced injury. This study was taken up to know the biomarker response to contrast administration in 58 diabetic and 59 nondiabetic male patients with same baseline parameters and baseline serum creatinine <1.2 mg/dl undergoing coronary angiography and their role in predicting the development of CIN. Serum creatinine, serum cystatin C, and urinary-NGAL (u-NGAL) were analyzed at baseline (0 h), 4 h, and 24 h after the administration of contrast medium. CIN was defined as a 25% increase in serum creatinine concentration from the baseline value or an absolute increase of at least 0.5 mg/dl within 48 h after the administration of contrast media. Serum creatinine rose 24 h after contrast administration in the diabetic group compared to 48 h in the nondiabetic group. Serum cystatin C levels rose 24 h after contrast administration in both the groups. The earliest marker to rise in both the groups was u-NGAL at 4 h. Diabetic patients had significantly higher u-NGAL (P = 0.005), and serum creatinine levels (P = 0.008) 4 h, and 24 h after contrast administration, respectively. Serum creatinine and u-NGAL/creatinine at 4 h were found to be the best predictors of CIN in the DM and non-DM patients, respectively. Biomarker response to contrast administration is different in diabetic and nondiabetic patients following contrast administration. Diabetic patients exhibit early and greater degree of renal impairment compared to the nondiabetic patients irrespective of the outcome. We propose the use of serum creatinine in patients with DM and u-NGAL/creatinine in non-DM patients to identify CIN as early as 4 h after contrast administration.

Evaluation of activity of hypothalamo-pituitary-gonadal axis in postmenopausal women suffering from severe acute illness.

BACKGROUND & OBJECTIVES: Postmenopausal women constitute an ideal model for studying the extent of hypothalamo-pituitary gonadal (HPG) axis suppression in critical illness as the gonadotropins are normally high and non-cyclical in them. The objective was to assess the impact of acute severe illness in postmenopausal women on the HPG axis and the activities of the hypothalamo-pituitary-adrenal (HPA), the hypothalamo- pituitary-thyroid (HPT) axes; and levels of serum prolactin, by comparison between critically ill postmenopausal women and otherwise healthy postmenopausal women. METHODS: Thirty five consecutive postmenopausal women older than 60 yr admitted to medical intensive care with a s0 implified a0 cute p0 hysiology s0 core II (SAPS II) more than 30 were included. On day five of their in-hospital stay, blood samples were collected for oestradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol, androstenedione, prolactin and thyroid profile. Thirty five apparently healthy postmenopausal women were selected as controls. RESULTS: Levels of LH, FSH, thyrotropin, free thyroxin (fT 4 ) and free tri-iodothyronine (fT 3 ) were lower while oestradiol, cortisol and dehydroepiandrosterone were higher among patients in comparison to healthy controls. Prolactin levels were similar in patients and controls. Among sick patients both FSH and fT 4 showed a negative correlation ( P<0.05) with the SAPS II score. INTERPRETATION & CONCLUSIONS: In critically ill postmenopausal women, paradoxically elevated oestrogen levels despite gonadotropin suppression suggests a non-ovarian origin. Prolactin remained unaltered in patients despite their illness, possibly reflecting atrophy of lactotrophs in menopause.

Utility of saliva as a sample to assess renal function and estimated glomerular filtration rate.

Diagnosis of renal diseases by assessing renal parameters in saliva. Biochemical investigations using serum form important component of monitoring patients with renal disease. Utility of saliva, in diagnosis and monitoring of patients with renal disease and for calculation of estimated glomerular filtration rate (eGFR), was studied. Sixty patients with renal disease and sixty ageand sex-matched healthy controls were studied. Urea, creatinine, sodium, potassium, uric acid, calcium, and phosphorus were measured in both serum and saliva. eGFR was calculated using salivary creatinine. Data were expressed as mean ± standard deviation. Comparison and correlation between groups were assessed by Student's t-test and Pearson correlation, respectively. Bland-Altman plot, mountain plot, and intra-class correlation coefficient were used to test agreement. A P <0.05 was considered statistically significant. Statistical analysis was done using Microsoft excel spreadsheets, Medcalc Version 10.0, and SPSS version 11.5. Salivary levels of urea, creatinine, uric acid, sodium, potassium, and phosphorus were higher in patients compared to controls. Potassium and phosphorus levels were higher (P = 0.001) and creatinine, sodium, calcium, and uric acid levels were lower (P = 0.001) in saliva compared to serum in both patients and controls. Positive correlation was observed between serum and salivary urea and creatinine (P < 0.0001). eGFR values calculated from salivary creatinine showed good agreement with those calculated form serum creatinine. Salivary urea (>6 mmol/L) and creatinine (>14.6 µmol/L) and eGFR calculated from salivary creatinine can be used to identify patients with renal disease.

Nitric oxide status in patients with chronic kidney disease.

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.

Ischemia-modified albumin levels in overt and subclinical hypothyroidism.

BACKGROUND: Free radical-mediated oxidative stress (OS) has been implicated in the pathogenesis of thyroid disorders. The ischemia-modified albumin (IMA) has been proposed as a marker of protein oxidative damage, which has been found to reflect hypoxic stress. AIM: Our aim was to evaluate IMA, malondialdehyde (MDA), and reduced glutathione (GSH) levels in patients with overt hypothyroidism (OHT) and subclinical hypothyroidism (SHT) in comparison to euthyroid controls. SUBJECTS AND METHODS: Albumin, IMA, IMA/albumin ratio, MDA, GSH, total cholesterol (TC), triglycerides (TG), HDL-Cholesterol were assessed in 105 subjects grouped into OHT, SHT patients, and euthyroid controls with 35 subjects in each group. RESULTS: MDA and IMA levels were significantly elevated while the GSH concentrations were significantly lower in OHT and SHT patients compared to controls (p < 0.01). When IMA values were normalized for albumin concentrations, the IMA/albumin ratio was also significantly elevated in both patient groups compared to controls (p < 0.01). These changes were more pronounced in the OHT group when compared to SHT group. In OHT group, thyroid-stimulating hormone (TSH) levels showed significant positive correlation with MDA (r = 0.470, p = 0.004), IMA (r = 0.530, p = 0.001), and IMA/albumin ratio (r = 0.525, p = 0.001). Both IMA (r = -0.342, p = 0.041), IMA/albumin ratio (r = -0.378, p = 0.023) showed significant negative correlation with GSH in OHT patients. No significant correlation between variables was, however, observed in SHT group. CONCLUSIONS: Increase of MDA and IMA levels with decreased antioxidant status indicate the presence of OS in hypothyroid patients, which was more pronounced in OHT patients. Elevated levels of IMA can be a clinically useful marker of protein oxidative damage and OS in hypothyroidism.

Subclinical atherosclerosis in patients with rheumatoid arthritis by utilizing carotid intima-media thickness as a surrogate marker.

BACKGROUND & OBJECTIVES: Patients with rheumatoid arthritis (RA) are more prone for accelerated atherosclerosis and Asian Indians as an ethnic group are predisposed to a high risk of premature atherosclerosis. However, sparse data are available regarding the burden of atherosclerosis among asymptomatic adult patients with RA in south India. We studied the burden of asymptomatic atherosclerosis in adult south Indian patients with RA at Tirupati, Andhra Pradesh, India, utilizing carotid intima-media thickness (CIMT) as a surrogate marker. METHODS: Ultrasound examination of the carotids and CIMT measurement (mm) were carried out in 32 patients with RA, 32 age- and gender-matched normal controls, and 32 patients with atherosclerosis and angiographically proven coronary artery disease. The CIMT values in patients with CAD and normal controls were used to derive the appropriate cut-off value of CIMT for defining atherosclerosis that would be applicable for the ethnic population studied. RESULTS: Patients with RA had a higher mean CIMT (mm) compared with normal control subjects (0.598 ± 0.131 vs 0.501 ± 0.081; p0 = 0.001). Carotid plaque was found more frequently among the cases compared with normal controls [5/32 (15.6%) vs 0/32 (0%), p0 =0.020]. Using this cut-off value derived by the receiver operator characteristic curve method (≥ 0.57 mm; sensitivity 84.4; specificity 90.6%) and the 75 th percentile value among normal controls (≥ 0.55 mm) as surrogate markers, the presence of subclinical atherosclerosis was significantly more among asymptomatic patients with RA compared with normal controls [(59.3 vs 12.5%; p0 <0.001) and (62.5 vs 25%; P<0.001) respectively]. INTERPRETATION & CONCLUSIONS: Based on the present findings CIMT appears to be a useful surrogate marker for detecting subclinical atherosclerosis in adult Indian patients with RA.