Selective decrease in alpha1-antitrypsin levels in diabetic retinopathy: Could the levels of it be playing a role in the pathophysiology of diabetic retinopathy?

Background & objectives: Type 2 diabetes mellitus (T2DM) is known to induce inflammation and activation of neutrophils causing the release of neutrophil elastase (NE), a pro-inflammatory proteinase. The activity of NE is regulated by endogenous inhibitors alpha1-antitrypsin (α1-AT) and alpha2-macroglobulin (α2-MG). Disrupted proteolytic homeostasis in T2DM patients is one of the causes for vascular complications. This study was carried out for evaluating the levels of plasma NE, α1-AT, α2-MG and NE-α1-AT complex to understand their roles in the pathophysiology of diabetic nephropathy (DN) and diabetic retinopathy (DR). Methods: A total of 240 participants (Control, n=60; T2DM, n=60; DN, n=60; and DR, n=60) were recruited after recording history, clinical examination and laboratory investigations. Retinopathy was confirmed by fundoscopy and nephropathy by urinary albumin excretion and serum creatinine levels. NE was measured using STANA. α1-AT, α2-MG and NE-α1-AT complex were estimated by ELISA. Results: Baseline clinical and laboratory findings were confirmatory to the study groups. The mean elastase activity was higher (P<0.0005) in diabetes groups (T2DM=0.73±0.31, DN=0.87±0.35, DR=0.76±0.41) than controls (0.35±0.20). The levels of α1-AT were lower in DR (8.77±2.85) than DN (26.26±6.16) and T2DM (41.13±14.06) when juxtaposed with controls (122.95±25.71). The approximate fold decrease of α1-AT levels was 15 for DR and four for DN compared to controls. The levels of α2-MG were lowered in T2DM (167.29±30.45), DN (144.66±13.72), and DR (104.67±11.47) than controls (208.87±31.16). The NE-α1-AT complex levels were: controls (215.83±13.61), T2DM (98.85±23.85), DN (129.26±20.40) and DR (153.25±17.11). Interpretation & conclusions: Homeostasis of NE, α1-AT and α2-MG is disrupted in T2DM, DN and DR. Strikingly reduced levels of α1-AT observed in DR are indicative of its possible role in the pathophysiology of retinopathy and emphasizes α1-AT as a plausible therapeutic target.

Plasma Neutrophil Elastase, α1-Antitrypsin, α2-Macroglobulin and Neutrophil Elastase-α1-Antitrypsin Complex Levels in patients with Dengue Fever.

Dengue fever (DF) is characterized by systemic inflammatory response including neutrophil activation leading to uncontrolled elastase activity. This study was aimed to measure the activity of plasma neutrophil elastase (NE), its endogenous inhibitors α1-antitrypsin (α1-AT) and α2-macroglobulin (α2-MG) and elastase in complex with α1-AT (NE-α1-AT complex) in DF. 50 dengue patients [39 DF and 11 dengue hemorrhagic fever (DHF)] and 52 healthy subjects were included in the study. NE was measured using N-succinyl-tri-alanine-p-nitroanilide as substrate. α1-AT, α2-MG and NE-α1-AT complex were estimated by ELISA. The result analysis indicated that the dengue patients had significantly higher elastase activity with significantly reduced inhibitor levels compared to controls. Between DF and DHF patients, DHF group had significantly higher elastase activity. In conclusion, significantly elevated NE and reduced inhibitors level in dengue fever indicate these parameters could be of significance in DF particularly for the assessment of progression of inflammatory processes.

Correlation of Plasma Neutrophil Elastase Activity and Endogenous Protease Inhibitor Levels with the Severity of Pre-eclampsia.

INTRODUCTION: Pre-eclampsia (PE) is a common maternal syndrome characterized by severe systemic inflammatory response including neutrophil activation leading to uncontrolled activity of elastase. The excessive activity of elastase would lead to destroyal of the integrity of endothelial cells and could exacerbate the pathophysiological symptoms in PE. Thus, assessment of NE activity and its control mechanisms would be of relevance in the determination of severity of PE. AIM: To correlate the activity of plasma NE and its endogenous inhibitors α1-antitrypsin (α1-AT) and α2-macroglobulin (α2-MG) with severity of PE. MATERIALS AND METHODS: A comparative study was conducted between normotensive pregnant (n=50) and pre-eclamptic (n=50) women. Serum C-Reactive Protein (CRP) was estimated by rapid latex slide and uric acid by uricase method. Plasma elastase was estimated using succinyl tri- L-alanyl-p-nitroanilide as substrate. Plasma α1-AT, α2-MG and NE- α1-AT complex were quantified by ELISA. ANOVA and Pearson's correlation tests were used to analyze the data. The results were expressed as mean±SD and p-value <0.001 was considered statistically highly significant. RESULTS: The activity of elastase was increased significantly in severe PE (0.62±0.08) in comparison to normal (0.35±0.10) and mild pre-eclamptic subjects (0.37±0.03). The values of α1-AT were significantly less in mild (83.94±25.08) and severe PE (68.58+26.39) in comparison to normal (110.26±42.39). There was a significant rise in the levels of α2-MG in severe PE. However, the complex estimation did not evince any significant changes. CONCLUSION: The results of the present study indicate a significantly elevated elastase activity, α2-MG levels and decreased α1-AT in severe PE patients. The correlation analyses of PE severity parameters with NE, α1-AT and α2-MG further support the roles of these molecules in the assessment of severity of PE.

Oxidant-antioxidant status in colorectal cancer patients-Before and after treatment.

Erythrocyte antioxidant glutathione and malondialdehyde levels in erythrocytes and plasma glutathione S-transferase levels were estimated in patients with colorectal cancer and compared to controls. Further, the patients underwent four weeks of radiotherapy with adjuvant chemotherapy. The same parameters were estimated after four weeks of radiotherapy and compared with pretreatment levels. It was observed that there was a decrease in erythrocyte glutathione and malondialdehyde levels in patients with colorectal cancer compared to controls, but not in case of GST. However, after chemoradiotherapy, there were no statistically significant differences in all the parameters studied.