Diagnosis of Amyloidosis: Clinicopathological Advances and Challenges

Amyloidosis is a systemic disease with different subtypes of misfolded, insoluble proteins, which are deposited in viscera and thereby cause damage to the affected organs. Its clinical manifestations are highly variable depending on the organs and tissue affected and often require a high degree of clinical suspicion to achieve correct diagnosis. Development of proteomic tools, radioisotope scintigraphy, immunologic antibody targets by immunohistochemistry, immunofluorescence and microscopic techniques have improved the sensitivity of accurate detection of specific subtypes of amyloid proteins. Newer therapeutic targets have been developed to arrest or suppress the specific types of amyloid proteins, giving rise to the possibility of targeted therapy with better quality of life and improved survival benefits for patients. AL, ATTR, AA and ALECT2 are the major subtypes of amyloidosis and kidney, heart, soft tissue, and peripheral nerves are the most affected viscera. The key to achieving success in better quality of life and overall survival in patients, is in early diagnosis and accurate subtyping of amyloidosis

Sub-chronic toxicological evaluation of cleistanthin A and cleistanthin B from the leaves of Cleistanthus collinus (Roxb.)

AbstractObjectiveTo investigate the toxicological effects of cleistanthin A and cleistanthin B using sub-chronic toxicity testing in rodents.MethodCleistanthins A and B were isolated from the leaves of Cleistanthus collinus. Both the compounds were administered orally for 90 days at the concentration of 12.5, 25 and 50 mg/kg, and the effects on blood pressure, biochemical parameters and histology were assessed. The dose for sub-chronic toxicology was determined by fixed dose method according to OECD guidelines.ResultSub-chronic toxicity study of cleistanthins A and B spanning over 90 days at the dose levels of 12.5, 25 and 50 mg/kg (once daily, per oral) revealed a significant dose dependant toxic effect in lungs. The compounds did not have any effect on the growth of the rats. The food and water intake of the animals were also not affected by both cleistanthins A and B. Both the compounds did not have any significant effect on liver and renal markers. The histopathological analysis of both cleistanthins A and B showed dose dependent morphological changes in the brain, heart, lung, liver and kidney. When compared to cleistanthin A, cleistanthin B had more toxic effect in Wistar rats. Both the compounds have produced a dose dependent increase of corpora amylacea in brain and induced acute tubular necrosis in kidneys. In addition, cleistanthin B caused spotty necrosis of liver in higher doses.ConclusionThe present study concludes that both cleistanthin A and cleistanthin B exert severe toxic effects on lungs, brain, liver, heart and kidneys. They do not cause any significant pathological change in the reproductive system; neither do they induce neurodegenerative changes in brain. When compared to cleistanthin A, cleistanthin B is more toxic in rats

Matrix metalloproteinase-9 is elevated and related to interleukin-17 and psychological stress in male infertility: A cross-sectional study

Background: Matrix metalloproteinase-9 (MMP-9), interleukin-17 (IL-17) and psychological stress are known to play a role in the pathogenesis of male infertility. Objective: To assess the association of MMP-9 with IL-17 and psychological stress in infertile men. Materials and Methods: In this cross-sectional study, 39 men with infertility diagnosed based on semen analysis and 39 subjects with normal semen analysis were included in the study. MMP-9 and IL-17 were estimated in both groups by ELISA. Perceived stress scale was used to assess psychological stress in controls and cases. Results: In infertile cases, MMP-9 and IL-17 were significantly increased when compared with controls (p = 0.046, p = 0.041 respectively). A significant association of MMP-9 was observed with IL-17 (r = 0.335, p = 0.037) and perceived stress scale (r = 0.329, p = 0.041). Conclusion: IL-17 and stress increase MMP- 9 levels in infertile men. Key words: Infertility, Interleukins, Peptide hydrolase

Effect of long acting insulin supplementation on diabetic nephropathy in Wistar rats

867-874<span style="font-size: 9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:" times="" new="" roman""="" lang="EN-GB">This study was designed to check whether insulin supplementation is crucial for inducing diabetic nephropathy (DNP) in Wistar rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin. The urinary biochemical parameters such as albumin, creatinine and urea nitrogen were monitored every two weeks. The histological changes in the kidney were observed at the end of both fifth and seventh month. Immunohistochemical analyses of VEGF, ERK-1 and NF-B expression were performed to demonstrate mesangial expansion and glomerulosclerosis, which are the defining histological features of nephropathy. A significant change in the urinary biochemistry was observed in diabetic animals at the end of four months, but the aforementioned quantitative changes were delayed in diabetic animals treated with insulin. At the end of seven months, the diabetic animals showed prominent histological changes such as glomerular basement membrane thickening, nodular glomerulosclerosis and mesangial expansion. However, these changes were not observed in diabetic animals treated with insulin even at the end of the study. From the results, it can be concluded that there is no need of insulin supplementation for inducing DNP, when the animals are induced with an optimal dose of 45 mg/kg body weight of streptozotocin. </span

Basal like carcinoma of breast in patient with neurofibromatosis I: An association or co-existence?

Neurofibromatosis I (NF I), an autosomal dominant disorder is associated with increased risk of benign and malignant peripheral nerve sheath tumors and central nervous system tumors. There are only few case reports of breast carcinoma in known patients of NF I. We report a case of basal like carcinoma of the breast in a 69-year-old lady who had NF I. Considering the rare association of carcinomas with NF I and finding that both the NF I gene and a breast cancer pre-disposition gene, BRCA 1 are located in close proximity on chromosome 17q makes the association of these two conditions intriguing

Phosphatase and tensin analog expression in arterial atherosclerotic lesions

Context: Phosphatase and tensin analog (PTEN) gene mutation has been proven for pro-inflammatory property and proliferative potential through tyrosine kinase pathway. We studied mutated PTEN for its pathogenetic association in arterial atherosclerosis. Aims: The objective was to study mutation of PTEN by immunohistochemical method in arterial atherosclerotic lesions and correlate with grades of atherosclerosis, smooth muscle migration in intima, degree of inflammation and Framingham heart study risk factors. Settings and Design: Human, Prospective Clinical study. Materials and Methods: We studied patients with arterial occlusive disease diagnosed by Doppler ultrasonography over a 2-year period. Immunohistochemistry was performed with mouse monoclonal antibodies for PTEN and smooth muscle actin (SMA). Statistical Analysis Used: Chi-square test. Results and Conclusion: Aorta was the single most common vessel affected (21%). Mean age of patients studied was 48.6 years and 80% were male. Mutant PTEN was associated with higher grades of atherosclerotic lesions (P < 0.0001) graded by American Heart Association classification and with smooth muscle proliferation and migration in intima (P < 0.0001). No statistically significant association with the vessel wall inflammation and other risk factors of atherosclerosis