Evaluation of oxidative stress,enzymatic and non-enzymatic antioxidants and metabolic thyroid hormone status in patients with diabetes mellitus

AimsOxidative stress is currently suggested as mechanism underlying diabetes and diabetic complications. The aim of the study was to evaluate the magnitude of oxidative stress in patients with diabetes by measuring the lipid peroxidation as well as the status of the antioxidant defense system, thyroid hormones status and other biochemical variables.MethodsThe study population consisted of 100 subjects divided into two groups viz. diabetic (n = 50) and healthy controls (n = 50).ResultsThe level of thiobarbituric acid reactive substances (TBARS) was found to be increased significantly in diabetic patients compared to healthy controls. On the other hand, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), reduced glutathione (GSH), vitamin A, vitamin E and vitamin C were found to be decreased significantly in diabetics when compared to control subjects. The level of TSH was significantly decreased whereas the levels of T4 and FT4 were significantly increased in diabetic patients than the control subjects. However, the T3 and FT3 levels did not differ significantly between groups.ConclusionOur findings indicate that changes in oxidant and antioxidant equilibrium will have biological and possibly pathological role in the development of secondary complications. The study has shown a high incidence of abnormal thyroid hormone status among the diabetics. In our findings demonstrate that detection of thyroid hormone status in the early stage of the disease will help the patients to improve quality of life and reduce the morbidity rate.     

Homocysteinethiolactone and Paraoxonase: Novel markers of diabetic retinopathy

OBJECTIVE

Paraoxonase (PON) exhibits esterase activity (PON-AREase) and lactonase activity (PON-HCTLase), which prevent LDL oxidation and detoxify homocysteine thiolactone (HCTL). The role of HCTL and PON-HCTLase as a risk factor for the microvascular complication in diabetic retinopathy at the level of vitreous has not been investigated.

RESEARCH DESIGN AND METHODS

Undiluted vitreous from patients with proliferative diabetic retinopathy (PDR) (n = 13) and macular hole (MH) (n = 8) was used to determine PON-HCTLase and PON-AREase activity spectrophotometrically. HCTL levels were detected by liquid chromatography–tandem mass spectrometry. In vitro studies were done in primary cultures of bovine retinal capillary endothelial cells (BRECs) to determine the dose- and time-dependent effect of HCTL and homocysteine (Hcys) on PON-HCTLase activity, as well as to determine mRNA expression of PON by RT-PCR.

RESULTS

A significant increase in HCTL and PON-HCTLase activity was observed in PDR compared with MH (P = 0.036, P = 0.001), with a significant positive correlation between them (r = 0.77, P = 0.03). The in vitro studies on BRECs showed a dose- and time-dependent increase in the PON-HCTLase activity and mRNA expression of PON2 when exposed to HCTL and Hcys.

CONCLUSIONS

This is the first study showing elevated levels of vitreous HCTL and PON-HCTLase activity in PDR. These elevations are probably a protective effect to eliminate HCTL, which mediates endothelial cell dysfunction. Thus, vitreous levels of HCTL and PON activity can be markers of diabetic retinopathy. The bioinformatics analysis reveals that the structure and function of PON that can be modulated by hyperhomocysteinemia in PDR can affect the dual-enzyme activity of PON.Hyperhomocysteinemia is a well-established independent risk factor for the development of macrovascular and microvascular diseases (1). Recent reports show that increased homocysteine thiolactone (HCTL) levels are associated with diabetic macrovasculopathy (2). HCTL is formed in all cell types as a result of error-editing met-tRNA synthetase when there is excess homocysteine (Hcys). The interaction of HCTL with proteins leads to protein homocysteinylation and loss of function (3). Therefore, detoxification of HCTL is crucial. This is possible by the lactonase (HCTLase) activity of paraoxonase (PON) (4). The enzyme PON is a calcium-dependent 45-kDa protein coded by chromosome 7q21-22. The PON gene family in humans has three members: PON1, PON2, and PON3. Whereas PON1 and PON3 are associated with serum HDL (5), PON2 is ubiquitously expressed in tissues (6). PON1 exhibits antioxidant properties, thereby preventing the accumulation of oxidized LDL, and PON2 acts mainly at the cellular level (7). Lipid oxidation plays a role not only in macrovascular diseases but also in microvascular dysfunction, and serum PON1 activity was decreased in patients with diabetic retinopathy (8). While elevated Hcys in the vitreous of patients with proliferative diabetic retinopathy (PDR) was reported by us and others (9,10), there are no reports on HCTL levels and PON activity. This study aims to detect the vitreous levels of HCTL, PON-HCTLase, and esterase (PON-AREase) activity in PDR case subjects and in in vitro studies in bovine retinal capillary endothelial cells (BRECs).     

Frequent attenders to the ED: patients who present with repeated asthma exacerbations

Background

Asthma has been reported as one of the main causes of frequent attendance to the emergency department (ED), and many of those visits are potentially preventable. Understanding the characteristics of frequent attender (FA) patients with asthmatic exacerbations will help to identify factors associated with frequent attendance and improve case management. The aim of this study is to describe the characteristics of FA who present multiple times to the ED for asthma exacerbations.

Methods

This study was a retrospective review of cases presented to Singapore General Hospital ED in 2010. Patients who attended the ED for 4 times or more with at least 1 visit attributable to asthma exacerbations in 2010 were included. They were then categorized as FA with multiple exacerbations (FAME) and those with fewer exacerbations.

Results

Of 105 616 ED patients, 155 patients attending the ED in 2010 were identified as FA with asthma, and 26 (17%) of these patients were classified as FAME, resulting in 213 visits (45% of total visits). Compared with FA with fewer exacerbations group, FAME were more likely to be men (P = .002), unemployed (P < .000), bad debtors (P = .045), substance abusers (P = .022), previously known to medical social workers (P = .002), and were found to spend a longer amount of time in the ED (> 6 hours) (P = .03).

Conclusion

We found that a small number of FAME patients accumulated a large number of ED visits and spent a significantly longer time in the ED. This group tended to be males with social, financial, and addiction problems.     

Adiposity measures as predictors of long-term physical disability

ObjectiveTo compare the predictive value of a variety of adiposity measures for the risk of disability.Design/settingThis study used 14-year follow-up of the Melbourne Collaborative Cohort Study (n = 7142). Adiposity measures were collected at baseline and disability measures for 5 self-care activities and mobility were collected at follow-up (2003–2007).MethodsLogistic regression was used to analyze the association between each adiposity measure (body mass index [BMI], waist circumference [WC], hip circumference, waist-to-hip ratio, fat mass, fat free mass, and percentage fat and disability. Area under the receiver operating curve ranking and comparison between nested models were used to determine the best predictor of disability.ResultsFor men and women, the odds for disability increased with increasing adiposity. In men, BMI was the most predictive adiposity measure for all types of disability. In women, 2 adiposity measures (BMI and WC) predicted overall and mobility disability better than only one measure, with hip circumference the single best predictor for self-care disability.ConclusionsBMI and WC predicted disability well in men and women. Identifying individuals at high risk of future disability through simple measures of adiposity will be essential if we are to adequately cater for our ageing population.     

Reye and Reye-like Syndromes: Result of a Pilot Stud in Peninsular Malaya, 1986

A pilot epidemiologic study of all cases of Reye and Reye-like syndromes was undertaken at 8 representative major hospitals in Peninsular Malaya from January 1st to December 31st 1986. The cases were classified as definitive Reye's syndrome, clinical Reye's syndrome and encephalo-hepatopathies. Less than 50% of cases reviewed fulfined the National Center for Disease Control criteria for clinical Reye's syndrome. Causes of Reye-like syndromes/encephalo-hepatopathies included fulminant hepatitis, Japanese B encephalitis, dengue, septicaemia, and complex febrile fits. It was not possible to differentiate clinical Reye's syndrome from the other encephalo-hepatopathies by either the clinical features (except for jaundice) or biochemical parameters. Liver biopsy is necessary for a definitive diagnosis of Reye's syndrome in Malaysia, because of the high prevalence of Reye-like diseases. The mortality rate in the 2 groups of patients is similar. Ingestion of salicylates was not found to be significantly associated with Reye and Reye-like syndromes in this study.     

Persistent hexavalent chromium exposure impaired the pubertal development and ovarian histoarchitecture in wistar rat offspring

Hexavalent chromium (CrVI) is a highly toxic metal and a major environmental pollutant. Several studies indicate that CrVI exposure adversely affects reproductive function. We reported that maternal Cr exposure resulted in Cr accumulation in the reproductive organs of female offsprings. CrVI can cross the placental barrier and also can be passed through breastfeeding. The present investigation aimed to determine the persistent (in utero through puberal period) CrVI exposure‐induced toxic effects on the reproductive functions of mother and the offspring. Induction of oxidative stress is one of the plausible mechanisms behind Cr‐induced cellular deteriorations. Mother rats exposed to CrVI showed reduced reproductive outcome, while the offsprings showed higher accumulation of Cr in ovary, altered steroid, and peptide hormones. Specific activities of antioxidant enzymes were decreased and associated with increased levels of H₂O₂, and lipid peroxidation. CrVI exposure also damaged the ovarian histoarchitecture in various age groups studied. CrVI exposure also delayed the sexual maturation. Results from the present investigation suggest that CrVI exposure from in utero through puberal period significantly damaged the pubertal development through altered antioxidants, anemia, and altered hormone levels. These changes were associated with damaged ovarian histoarchitecture and extended estrous cycle in developing Wistar rats. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 814–828, 2014.