Role of reactive oxygen species in pathogenesis of nephrotic syndrome

Nephrotic syndrome is the common chronic disorder characterized by alteration of permeability of the glomerular capillary wall, resulting in its inability to restrict the urinary loss of proteins. Nephrotic syndrome is characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia associated with peripheral edema. The molecular basis of glomerular permselectivity remains largely unknown. In recent years it has been proposed that Nephrotic syndrome is a consequence of an imbalance between oxidant and antioxidant activity. The present study was aimed to test that the reactive oxygen species are the mediators of excessive protein permeability and other complications of Nephrotic syndrome. For this 30 adults with Nephrotic syndrome were studied. The control group comprised 30 healthy adults matched for age. Serum levels of lipid peroxides, nitric oxide (NO⊙), α- tocopherol, ascorbic acid, erythrocyte superoxide dismutase activity, serum albumin, uric acid, cholesterol and plasma total antioxidant capacity were measured. Student’s ‘t’ test was applied for statistical analysis. There was a significant increase in lipid peroxide (1.58 ± 0.42 in controls, 3.64 ±1.3 in patients) (P<0.001) levels in study group as compared with controls. α-tocopherol (12.95 ± 1.04 in controls, 9.93 ± 1.43 in patients) (P<0.001), erythrocyte SOD activity(1.88 ± 0.9 in controls 1.07 ± 0.5 in patients) (P=0.01), serum albumin(4.06 ± 0.50 in controls, 3.04 ± 0.11 in patients) (P<0.001), and plasma total antioxidant capacity (847.33 ± 126.83 in controls, 684.00±102.94 in patients) (P<0.001) were significantly decreased. There was non-significant increase in uric acid (P>0.05), a non-significant decrease in NO⊙ (38.48 ± 15.47 in controls 37.47 ± 14.27 in patients) (P>0.05) and ascorbic acid levels ascorbic acid,( 0.95 ± 0.31in controls 0.79 ± 0.30 in patients) (P>0.05) in study group as compared with controls. Imbalance between oxidants and antioxidants may contribute to pathogenesis of proteinuria and related complications in nephrotic syndrome.     

Biochemical markers of liver and kidney function are influenced by thyroid function-a case-controlled follow up study in Indian hypothyroid subjects

Thyroid hormones regulate the renal hemodynamics and basal metabolic rate of most cells. This hospital-based case-control study was done to evaluate the changes in biochemical markers of liver and kidney function in hypothyroid subjects before and after treatment. The study included 176 subjects randomly selected from Thyroid clinics. Serum T₃, T₄, TSH, Liver and Kidney Function tests were analysed using standard kits. Forty-six hypothyroid patients were re-evaluated 6 weeks after thyroxine substitution therapy. Hypothyroid subjects (n=80) showed significantly raised serum creatinine and uric acid levels as compared to euthyroid subjects (n=96). After 6 weeks of thyroxine replacement, serum creatinine and uric acid decreased significantly and were comparable to euthyroid group. A positive correlation of ALT, AST, uric acid, protein and albumin with TSH levels (p<0.05) and negative correlation of serum T₄ levels with ALT, AST, proteins (p<0.05) was observed in the hypothyroid group. Hypothyroidism results in reversible impairment of hepatorenal function.     

C-Reactive Protein and Uric Acid Levels in Patients with Psoriasis

Serum CRP and uric acid levels were estimated in twenty-five patients with psoriasis (group III) before and after 12 weeks of treatment. Results were compared with a group of 25 normal subjects (group I) and a group of 25 patients of various skin diseases other than psoriatic lesion (group II). Mean value for CRP was found to be increased by more than 20 folds in patients with psoriasis, which was subsequently reduced to nearly 50% of the initial value after 12 weeks of treatment. These patients also showed hyperuricemia. Nearly 25% of these patients also exhibited arthritis. It is thus suggested that both CRP and uric acid levels should be monitored in patients with psoriasis.     

hs-CRP: A potential marker for hypertension in Kashmiri population

Hypertension is the most important public health problem in developing countries and one of the major risk factors for cardiovascular diseases, and it has been reported that hypertension is in part an inflammatory disorder and several workers have reported elevated levels of CRP in hypertensive individuals. The main aim of the present study was to evaluate the association between blood pressure and serum CRP levels across the range of blood pressure categories including prehypertension. A total of 104 patients and 63 control subjects were included in the present study. The level of CRP in the serum samples was estimated by a high sensitivity immunoturbidometric assay. Standard unpaired student’s ‘t’ test was used for comparison of hs-CRP levels between hypertensive patients and normotensive control subjects and between patient groups with different grades of hypertension and different durations of hypertensive histories. The mean serum hs-CRP level in hypertensive patients was 3.26 mg/L compared with 1.36 mg/L among normotensive control subjects (P<0.001). On comparison with normotensive control subjects, the hs-CRP levels vary significantly both with grades and duration of hypertension, with most significant difference found in patients with prehypertension (P<0.001), followed by Stage-I (P=0.01) and Stage-II(P=0.02) hypertensives. Significant difference in hs-CRP levels was also found in patients with shorter duration of hypertensive history (≤ 1year) when compared with those with ≥5 years of hypertensive history (P<0.01). Our study reveals a graded association between blood pressure and CRP elevation in people with hypertension. Individuals with prehypertension or with shorter duration of hypertension (≤1 Year) had significantly a greater likelihood of CRP elevation in comparison to chronic stage-I or stage-II hypertensives.     

提高综合医院焦虑障碍与抑郁障碍的识别率

目的:通过对南充综合医院门诊病人的抑郁障碍和焦虑障碍的发生率及共病现象研究,提高焦虑障碍与抑郁障碍的识别率。方法:随机抽取1000例门诊患者进行焦虑自评量表(SAS)和抑郁自评量表(SDS)的问卷调查,通过数据统计分析,阳性筛查焦虑障碍和抑郁障碍的患病情况。结果:门诊中有8.56%的患者存在焦虑障碍,6.03%的患者存在抑郁障碍,2.96%的患者存在焦虑障碍与抑郁障碍共病现象。女性焦虑障碍患病率大于男性患病率,女性抑郁障碍患病率大于男性患病率。结论:综合医院提高焦虑障碍与抑郁障碍的识别率的过程中应注意性别的影响,加强综合门诊对焦虑障碍及抑郁障碍的识别率。     

Total antioxidant capacity and lipid peroxidation in liver transplantation

Liver transplantation is an accepted therapy for chronic liver disease patients. These patients generally have low levels of fat soluble vitamins, which have important antioxidant roles. Therefore, this study was undertaken to investigate whether such patients had evidence of antioxidant depletion and increased lipid peroxidation before transplant and whether the subsequent ischemia and reperfusion encountered during liver transplantation have any effect on antioxidant levels and lipid peroxidation. We assessed plasma total antioxidant capacity and serum lipid peroxide in 12 patients undergoing liver transplantation and equal numbers of healthy subjects. We found that before reperfusion, antioxidant levels were significantly decreased along with significantly elevated lipid peroxidation levels as compared with healthy controls (P<0.001). On reperfusion of the liver graft, further declined values of total antioxidant accompanied with highly elevated lipid peroxidation were seen than those of pre-reperfusion samples (P<0.001). This data shows that patients undergoing liver transplant have lowered antioxidant defenses and evidence of free radical damage, which compound the additional insult of reperfusion injury. Therefore antioxidant therapy in these patients before transplantation may ameliorate the effects of reperfusion.     

Study of oxidative stress in obsessive compulsive disorder in response to treatment with Fluoxetine

Oxidative stress has been found to play important role in several neuropsychiatric diseases including Obsessive Compulsive Disorder. A longitudinal case control study was conducted to evaluate the oxidative stress in 30 newly diagnosed obsessive compulsive disorder patients and same number of control patients. Serum thiobarbituric acid reacting substances, plasma ascorbate were assessed to evaluate oxidative stress and Yale Brown obsessive compulsive scale for disease severity before and after treatment with Fluoxetine at the average dosage of 40 mg/day. Improvement in Yale Brown obsessive compulsive scale score by about 43% after 12 weeks treatment was associated with significantly decreased thiobarbituric acid reacting substances and increased plasma ascorbate values (p < 0.05). The newly diagnosed obsessive compulsive disorder patients had higher serum thiobarbituric acid reacting substances as well as a lower plasma ascorbate levels than the control population. Thus, the present study suggested a significant role of oxidative stress in obsessive compulsive disorder and showed that a successful treatment with Fluoxetine not only improves the clinical scenario but also reduces the oxidative stress that may further improve the prognosis of the disease.     

Evaluation of oxidative stress in pregnancy induced hypertension

This work was undertaken to investigate correlation between oxidative stress and initiation of pathogenesis of pregnancy induced hypertension (PIH). Fifty primigravidae in age group of 20–35 years and gestational age 28–42 weeks with PIH were taken as cases. Twenty healthy primigravidae with no medical and surgical complications of pregnancy and with blood pressure ≤140/90 mm Hg served as controls. The cases were again subgrouped as severe preeclampsia (12 in number) and mild pre-eclampsia (38 in number). All of them were evaluated for serum malondialdehyde (MDA), Serum vitamin E and plasma vitamin C levels. The serum MDA levels were raised significantly in women with mild preeclampsia (P<0.01) and in women with severe preeclampsia (P<0.01) in comparison to normal primi gravida. The serum vitamin E levels were decreased in primi gravida with mild preeclampsia (p<0.1) and in primi with severe pre eclampsia (P<0.1) in comparison to normal primi gravida but the fall was not statistically significant. There was a significant fall (P<0.05) in the vitamin C levels in primi with mild preeclampsia than in the normal primi. The vitamin C levels in severe preeclamptic patients were lower than the normal primi but the fall was not statistically significant (P=0.10). The serum MDA and vitamin E showed a negative correlation in all the cases. The serum MDA and plasma vitamin C also showed a negative correlation in the control and study group. This observation suggests that in hypertensive disorders of pregnancy there is an imbalance between lipid peroxidation and antioxidant vitamin status because of oxidative stress. The decreased serum concentrations of the antioxidant vitamins supports the hypothesis that lipid peroxidation is an important causative factor in the pathogenesis of preeclampsia. The rise in antioxidants is probably to compensate the increased peroxide load in severe preeclampsia.     

Changes in levels of serum glycoproteins in major depressive disorders

The present study deals with estimation of levels of fractions of serum glycoproteins, protein bound hexose (PBH), protein bound hexosamine (PBHex), protein bound fucose (PBF), protein bound sialic acid (PBS) and protein bound carbohydrate (PBC) in thirty patients of Major Depressive Disorders (MDD) in comparison with thirty normal subjects. In patients of MDD, the level of PBH, PBHex, PBF, PBS and PBC were significantly higher as compared to the normal subjects (p<0.05). In patients, of MDD, after one-month treatment with fluoxetine, the levels of PBH, PBHex, PBF, PBS and PBC were significantly decreased as compared to the levels of these fractions in same patients of MDD before beginning of the treatment (p<0.05). Based on findings of the present study, it can be concluded that changes in the level of serum glycoproteins level before and after treatment with fluoxetine can be correlated with clinical status of MDD.     

Uric acid a better scavenger of free radicals than vitamin C in rheumatoid arthritis

Uric acid an endogenous aqueous antioxidant in normal humans is present in much higher concentrations than vitamin C and has been known to cover 2/3^rd of the free radical scavenging capacity in plasma. In the present study average uric acid levels of patients of rheumatoid arthritis were found to be close to the normal individuals. A unique feature was observed after classifying the patients on the basis of the duration of suffering, the patients having longer duration of disease had least uric acid levels as compared to those suffering from relatively lesser period, similar trend was observed in the ascorbic acid estimations. The decline in uric acid values with progression of the disease was much more than what was observed in case of ascorbic acid suggesting the significant role of uric acid in scavenging of free radicals. Too much lowering of Uric Acid should be checked and vitamin C should be supplemented in diet for maintaining the balance between pro oxidant and antioxidant forces to check pro oxidant insult in rheumatoid arthritis.     

Oxidative Stress-Induced Response of Some Endogenous Antioxidants in Schizophrenia

Reactive oxygen species (ROS) formed in various metabolic reactions cause unlimited damage by attacking and oxidizing the macromolecules. An arsenal of antioxidant substances neutralizes these ROS at various sites of their metabolic cascade, and if disequilibrium exists between the pro and antioxidant system, oxidative stress persists. The present study was undertaken in schizophrenia, to highlight the response and role of some endogenous antioxidants viz. reduced glutathione (GSH), bilirubin, total proteins, albumin and uric acid in scavenging the ROS. The effect of severity of disease, age factor, and substance abuse was also studied. In all, 50 schizophrenics and 50 age and sex-matched controls were enrolled in the present study. Fasting blood samples were drawn for estimating malondialdehyde (MDA), GSH, bilirubin, total proteins, albumin and uric acid in both the groups. The results were statistically analyzed by Z-test and correlated using correlation coefficient (r). The study shows reduction in MDA levels and decline in the level of endogenous antioxidants, but within the normal range. Chronic schizophrenics were at a higher risk of oxidative stress and age and substance abuse seems to worsen the situation.     

Reversal of haemodialysis induced hypertriacylgycerolemia by L-carnitine

A 24 week follow-up study on lipid change following maintenance haemodialysis (MHD) in 25 chronic renal failure (CRF) patients revealed significantly raised serum Triacylglycerol (TAG) levels in these cases (P<0.001), while cholesterol and HDL-Cholesterol did not show any significant change, the extent of increase was 10.5±3.6% after 12 weeks and 23.0±5.8% after 24 weeks. Corresponding increase in CRF patients treated conservatively, without haemodialysis, were 3.1±1.2% and 7.2±2.7% at these intervals. Subsequent oral administration of L-Carnitine (5mg/kg body weight twice a day) for three weeks brought about a significant reversal of elevated serum TAG level in MDH group as well as in the conservatively treated group (P≤0.05). It is concluded that the haemodialysis induced Hyper-Triacylglycerolemia of CRF patients is revertible by Carnitine replenishment. Even the concomitant increase in conservatively treated group is revertible by carnitine administration.     

Correlation between Apgar score and urinary uric acid to creatinine ratio in perinatal asphyxia

A randomized case control hospital based study was conducted over 12 months time on 31 asphyxiated and 31 normal newborn to see whether urinary uric acid can be used as a marker of perinatal asphyxia and can be correlated with the clinical diagnosis by Apgar score. Uric acid and creatinine were estimated in spot urine within 24 hours after birth in both cases and controls. A ratio between concentrations of uric acid to creatinine was estimated and compared between cases and controls. It was found that the ratios were significantly higher in cases than controls (3.1± 1.3 vs 0.96± 0.54; P < 0.001) and among asphyxia patients, a significant negative linear correlation was found between the uric acid to creatinine ratio and the Apgar score (r = −0.857, P < 0.001). So urinary uric acid to creatinine ratio can be used as an additional non-invasive dispace, easy and at the same time early biochemical marker of birth asphyxia which biochemically supports the clinical diagnosis and severity grading of asphyxia by Apgar score.     

Role of Oxidative Stress in Various Stages of Psoriasis

Psoriasis is a chronic inflammatory, proliferative skin disease characterized by pathological skin lesions due to various exogenous and endogenous factors. It is associated with a number of biochemical and immunological disturbances. Recently, it has been suggested that increased reactive oxygen species (ROS) production and compromised function of antioxidant system may be involved in the pathogenesis of this disease. In the present study, 90 psoriasis patients were selected. Disease severity was assessed by psoriasis area severity index score and grouped as mild, moderate and severe (each group consists of 30 subjects) and compared with 30 healthy controls. Serum levels of malondialdehyde, nitric oxide end products and the activities of antioxidant enzymes such as erythrocyte-superoxide dismutase, catalase and total antioxidant status were investigated in these groups/subjects. As compared to controls, we found severitywise significantly increased serum malondialdehyde, nitric oxide end products with decrease in erythrocyte-superoxide dismutase activity, catalase activity and total antioxidant status in patients with psoriasis suggesting worsening of the disease. It seems to be linked with the enhancement of Reactive Oxygen Species production and decreased antioxidant potential in psoriasis.     

Effect of oral antioxidant supplementation on lipid peroxidation during radiotherapy in head and neck malignancies

The objectives of the present study were to ascertain the variations in the serum levels of malondialdehyde and total antioxidant status, in head and neck malignancies with different stages, with and without oral antioxidant supplementation, before and after radiotherapy, and to validate the protective effects of an antioxidant supplementation during radiotherapy. The pretreatment values of serum malondialdehyde were significantly raised, while that of serum total antioxidant status were significantly declined in all the stages of head and neck malignancies, when compared with the healthy controls values (P<0.001). A significant correlation was observed related to the studied parameters and different stages of the disease. The study suggests that an oral antioxidant supplementation during radiotherapy is an effective mode in reducing oxidative stress. Antioxidant supplementation during radiotherapy may serve as an adjuvant therapy in malignancies offering a protection to normal cells that may further reduce the risk of developing secondary cancers.     

Oxidants and antioxidants in hypoxic ischaemic encephalopathy

In the present study, the role of serum lipid peroxide and serum nitric oxide as oxidants and erythrocytic superoxide dismutase & serum vitamin E as antioxidants were determined in the 50 neonates with hypoxic ischaemic encephalopathy. (HIE) as against 25 healthy neonates as controls 50 patients of HIE were further divided into two groups i. e. mild and moderate HIE patients. All subjects were in the age group of 37–41 weeks of gestation. The levels of serum lipid peroxide, serum nitric oxide and erythrocytic superoxide dismutase were significantly elevated in both groups of neonates with HIE than those of controls (P<0.001), whereas serum vitamin E levels were significantly decreased in both groups of HIE patients than those of controls (P<0.001). A positive correlation was obtained between serum lipid peroxide and erythrocytic superoxide dismutase (r=+0.86). Alterations in the status of oxidants and antioxidants indicate role of free radicals in the development of HIE.     

Beneficial Effect of Aqueous Garlic Extract on Inflammation and Oxidative Stress Status in the Kidneys of Type 1 Diabetic Rats

One of the most important complications of diabetes is nephropathy. This study investigates the effects of aqueous garlic extract on inflammation and oxidative stress status in the kidneys of diabetic rats. Male rats were divided into four groups- control rats, diabetic rats, garlic extract-treated diabetic rats, garlic extract-treated normal rats. The glucose, urea, uric acid, and creatinine levels were measured in sera using colorimetric methods. To determine the oxidative stress condition in the kidney tissues, total antioxidant capacity (TAC), malondialdehyde (MDA), and total oxidant status (TOS) were measured using colorimetric methods. Inflammation status was evaluated by the determination of tumor necrosis factor-alpha (TNF-α) gene and protein expression using qRT-PCR and ELISA respectively, while nitric oxide (NO) level in these tissues was measured using the Griess method. Histological examination of Kidneys was carried out by H&E staining. The levels of glucose, urea, and uric acid were found to increase in the serum of diabetic rats and decrease in that of diabetic rats after treatment with garlic. Measurement of MDA, TOS, and TAC revealed oxidative stress in diabetic rats, which improved after receiving the extract. The NO and TNF-α protein levels in diabetic rats were higher than those in control rats. After treatment with garlic, the levels of TNF-α protein and NO became close to the normal levels. Histological results confirmed certain other data as well. Garlic has antioxidant properties; therefore, it can reduce oxidative stress, which plays an important role in the development of diabetic nephropathy. Reduction in oxidative stress has beneficial effects on inflammation because it leads to a decrease in the level of TNF-α.     

Platelet factor 3 availability time,plasma phenol and phenolic acids in patients with uremia

Platelet factor 3 availability time (PF3 AT), Prothrombin time (PT), Plasma phenol, phenolic acids, blood urea and serum creatinine were estimated in 31 uremic patients. Significant increase (P<0.01) in PF3 AT and plasma phenolic acid was seen in 100 per cent of cases, while the increase in plasma phenol was seen in 90.3% of cases. The increase in PF3 AT was not uniformly proportional to the increase in plasma phenol or phenolic acids in all cases. Increase in PF3 AT was significant in cases of uremia with bleeding diathesis compared to the cases without bleeding diathesis. Increase in PF3 AT after addition of phenol and urea together to normal platelet rich plasma (PRP) in vitro was greater than the increase in PF3 AT after the addition of phenol or urea alone. Significant decrease (P<0.01) in PF3 AT, plasma phenol, plasma phenolic acids, blood urea and serum creatinine was seen in uremic patients after haemodialysis indicating that the retained toxic metabolites which increase PF3 AT are dializable substances.     

Circadian Periodicity of Circulating Plasma Lipid Peroxides,Uric Acid and Ascorbic Acid in Renal Stone Formers

Circadian periodicity of plasma lipid peroxides and serum ascorbic acid and uric acid levels were studied in one hundred renal stone formers (55 women and 45 men; age 20–60 years) and 50 clinically healthy volunteers (21 women and 29 men; age 21–45 years) with diurnal activity from 06:00 to 22:00 and nocturnal rest. A marked circadian variation was demonstrated by population-mean-cosinor for all studied variables in stone formers and healthy subjects. By comparison to the healthy controls, parameter tests indicate that the stone formers had a higher MESOR (±SE) of MDA (2.90 ± 0.03 vs. 2.28 ± 0.06; F = 94.929, p < 0.001), a lower MESOR of serum ascorbic acid (0.722 ± 0.010 vs. 0.839 ± 0.10; F = 32.083, p < 0.001), and a similar MESOR of serum uric acid. Furthermore, the patients also differed from the healthy subjects in terms of their circadian amplitude and acrophase (tested jointly) of all three variables (p < 0.001). The demonstration herein of a circadian rhythm in MDA, serum ascorbic and uric acid suggests that these variables could also serve as markers to optimize the timing of treatment and to assess the patient’s response to treatment for further management.     

Evaluation of the changes in serum iron levels in pre-eclampsia

Serum iron levels were studied in 50 patients with pre-eclampsia and the results were compared with 50 control cases. Their serum iron levels were found to be higher than the controls. Increase in serum iron was directly proportional to the increased levels of uric acid, urea and creatinine. Mean reticulocyte counts, plasma free haemoglobin and unconjugated bilirubin levels were also higher in these patients. It is suggested that haemolysis may be a major contributory factor for the increased levels of serum iron in pre-eclampsia.