Suganthy Rabi

Melatonin attenuates methotrexate‐induced oxidative stress and renal damage in rats

Nephrotoxicity is an adverse side effect of methotrexate (MTX) chemotherapy. The present study verifies whether melatonin, an endogenous antioxidant prevents MTX‐induced renal damage. Adult rats were administered 7 mg/kg body weight MTX intraperitoneally for 3 days. In the melatonin pretreated rats, 40 mg/ kg body weight melatonin was administered daily intraperitoneally 1 h before the administration of MTX. The rats were killed 12 h after the final dose of MTX/vehicle. The kidneys were used for light microscopic and biochemical studies. The markers of oxidative stress were measured along with the activities of the antioxidant enzymes and myeloperoxidase activity in the kidney homogenates. Pretreatment with melatonin reduced MTX induced renal damage both histologically and biochemically as revealed by normal plasma creatinine levels. Melatonin pretreatment reduced MTX induced oxidative stress, alteration in the activity of antioxidant enzymes as well as elevation in myeloperoxidase activity. The results suggest that melatonin has the potential to reduce MTX induced oxidative stress, neutrophil infiltration as well as renal damage. As melatonin is an endogenous antioxidant and is non‐toxic even in high doses it is suggested that melatonin may be beneficial in minimizing MTX induced renal damage in humans. Copyright

Protective effect of aminoguanidine against oxidative stress and bladder injury in cyclophosphamide-induced hemorrhagic cystitis in rat

Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major dose limiting side effect of CP. Recent studies show that aminogaunidine, an inhibitor of inducible nitric oxide synthase is a potent antioxidant and prevents changes caused by oxidative stress such as depletion of antioxidant activity and tissue injury. The purpose of the study is to investigate the effect of aminoguanidine on parameters of oxidative stress, antioxidant enzymes and bladder injury caused by CP. Adult male rats were randomly divided into four groups. Control rats were administered saline; the AG control group received 200 mg/kg body wt of aminoguanidine; The CP group received a single injection of CP at the dose of 150 mg/kg body wt intraperitoneally. The CP + AG group received aminoguanidine (200 mg/kg body wt) intraperitoneally 1 h before the administration of CP. The rats were sacrificed 16 h after CP/saline administration. The bladder was used for light microscopic studies and biochemical studies. The markers of oxidative damage including protein carbonyl content, protein thiol, malondialdehyde and conjugated dienes were assayed in the homogenates along with the activities of the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase and glutathione S transferase. In the bladders of CP treated rats edema of lamina propria with epithelial and sub‐epithelial hemorrhage was seen. All the parameters of oxidative stress that were studied were significantly elevated in the bladders of CP treated rats. The activities of the antioxidant enzymes were significantly lowered in the bladders of CP treated rats. Aminoguanidine pretreatment prevented CP‐induced oxidative stress, decrease in the activities of anti‐oxidant enzymes and reduced bladder damage. The results of the present study suggest the antioxidant role for aminoguanidine in CP‐induced bladder damage. Copyright

Protective effect of aminoguanidine against cyclophosphamide-induced oxidative stress and renal damage in rats

Abstract Background Cyclophosphamide (CP) is widely used in the treatment of tumors and B-cell malignant disease, such as lymphoma, myeloma, chronic lymphocytic leukemia, and Waldenstroms macroglobulinemia. Renal damage is one of the dose-limiting side effects of CP. Oxidative stress is reported to play important roles in CP-induced renal damage. Aim To find out whether aminoguanidine (AG) protects against CP-induced oxidative stress and renal damage. Method Renal damage was induced in the rats by administration of a single injection of CP at a dose of 150 mg/kg body weight intraperitoneally. For the AG pretreatment studies, the rats were injected intraperitoneally with AG at a dose of 200 mg/kg body weight 1 hour before administration of CP. The control rats received AG or saline alone. All the rats were killed 16 hours after the administration of CP or saline. The kidneys were used for histological examination by light microscopy and biochemical assays — malondialdehyde, protein carbonyl content, reduced glutathione (GSH), and the activities of antioxidant enzymes including glutathione peroxidase (GPx), glutathione S transferase (GSTase), catalase, glutathione reductase, and myeloperoxidase (MPO), a marker of neutrophil infiltration. Results Pretreatment with AG attenuated CP-induced renal damage histologically. Pretreatment with AG prevented CP-induced lipid peroxidation, protein oxidation, depletion of reduced GSH, and loss of activities of the antioxidant enzymes including GPx, catalase, and GSTase and also MPO activity. Conclusion The results of the present study reveal that AG can prevent CP-induced renal damage by inhibiting oxidative stress. Thus, AG may be useful for prevention of the nephrotoxicity of CP.

Light-weight plastination.

Plastination is an excellent technique which helps to keep the anatomical specimens in a dry, odourless state. Since the invention of plastination technique by von Hagens, research has been done to improve the quality of plastinated specimens. In this paper, we have described a method of producing light-weight plastinated specimens using xylene along with silicone and in the final step, substitute xylene with air. The finished plastinated specimens were light-weight, dry, odourless and robust. This method requires less use of resin thus making the plastination technique more cost-effective. The light-weight specimens are easy to carry and can easily be used for teaching.

Aminoguanidine, Selective Nitric Oxide Synthase Inhibitor, Ameliorates Cyclophosphamide-induced Hemorrhagic Cystitis by Inhibiting Protein Nitration and PARS Activation

OBJECTIVES To elucidate the mechanism by which aminoguanidine (AG) protects against cyclophosphamide (CP)-induced hemorrhagic cystitis. METHODS Hemorrhagic cystitis was induced in the rats by administration of a single injection of CP at a dose of 150 mg/kg body weight intraperitoneally. For the AG pretreatment studies, the rats were injected intraperitoneally with AG at a dose of 200 mg/kg body weight 1 hour before administration of CP. The control rats received AG or saline alone. All the rats were killed 16 hours after the administration of CP or saline. RESULTS Pretreatment with AG ameliorated CP-induced bladder damage. Pretreatment with AG prevented CP-induced elevation in nitrate levels, nitration of protein tyrosine, poly (adenosine diphosphate ribose) polymerase (PARP) activation, and restored the activity of superoxide dismutase, the peroxynitrite-sensitive enzyme. The results of the present study have confirmed that AG is effective in preventing CP-induced cystitis and have also demonstrated that the protective effect is from its ability to inhibit nitric oxide-induced protein nitration and poly (adenosine diphosphate ribose) polymerase activation. CONCLUSIONS AG can prevent CP-induced urotoxicity and lead to better tolerance of the drug. Thus, a more efficient and comfortable therapy can be achieved for patients in need of CP treatment. AG appears to be a promising drug for the prevention of the urotoxicity of CP.

Aminoguanidine, a Selective Nitric Oxide Synthase Inhibitor, Attenuates Cyclophosphamide-Induced Renal Damage by Inhibiting Protein Nitration and Poly(ADP-Ribose) Polymerase Activation

Background: Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Renal damage is one of the dose-limiting side effects of CP. Recent studies show that nitrosative stress plays an important role in CP-induced renal damage. Aim: The purpose of our study was to investigate whether aminoguanidine (AG), a selective inducible nitric oxide synthase inhibitor, protects against CP-induced nitrosative stress and renal damage. Method: Renal damage was induced in rats by administration of a single injection of CP at a dose of 150 mg/kg body weight intraperitoneally. For the AG pretreatment studies, the rats were injected intraperitoneally with AG at a dose of 200 mg/kg body weight 1 h before administration of CP. The control rats received AG or saline alone. All the rats were killed 16 h after the administration of CP or saline. Pretreatment with AG prevented CP-induced nitration of protein tyrosine and poly(ADP-ribose) polymerase (PARP) activation. Result: Pretreatment with AG attenuated CP-induced renal damage. The present study demonstrates that AG is effective in preventing CP-induced renal damage and also that the protective effect is from its ability to inhibit nitric oxide-induced protein nitration and PARP activation. Conclusion: The present study shows that AG can prevent CP-induced renal damage by inhibiting protein tyrosine nitration and PARP activation. Thus, a more efficient and comfortable therapy can be achieved for patients in need of CP treatment. AG appears to be a promising drug for the prevention of nephrotoxicity of CP.

Different subsets of Langerhans cells in human uterine tubes and uterus

Langerhans cells (LC) are antigen‐presenting cells present in tissues with high antigenic exposure. Their role in the upper female reproductive tract is not fully understood. This study aims to determine the distribution and morphology of LC in the normal and post‐partum human uterine tubes and uterus by staining with the specific LC markers, CD1a and zinc iodide‐osmium (ZIO), and to determine their association with helper and cytotoxic T cells.

Oblique sectional planes of block plastinates eased by Sac Plastination

To find an oblique cutting plane of a plastinate, e.g. to cut gamma-nails in the femur, the Block Plastination technique was modified. After CT and MRI examination, the specimens were plastinated with the standard resin mixture E6/E12/E600. Instead of using a box to form a block during the casting and curing stage, we embedded the specimen in a sac made of polyester foil. A polymerized wooden block was attached to the specimen. The sac was wrapped with tape to the embedded specimen with the block. This approach limited the amount of required resin to the inner volume of the plastinate. Then, the plastination sac was put in the incubator for further polymerization and curing. When the foil was removed from the plastinated specimen, the wooden block served as a socket for the grip when sawing. The outer shape of the specimen remained visible. Doing so, the adequate cutting plane could be determined easily.

Morphological Study of Dendritic Cells in Human Cervix by Zinc Iodide Osmium Method

BACKGROUND Dendritic cells (DCs) are a heterogeneous population of antigen presenting cells that have been identified in several tissues including the female reproductive organs. The aim of the present study is to demonstrate the morphological differences of dendritic cells in normal human exocervix using the Zinc Iodide Osmium (ZIO) procedure. MATERIALS AND METHODS Normal cervical tissues obtained from nine patients who underwent abdominal hysterectomies for various ailments were processed for histochemical study. Six microns thick serial sections were taken and viewed under a light microscope. The diameters of the cells were measured under a magnification of 40x using the Cellsens image analysing software and analysed using SPSS version 16. RESULTS AND CONCLUSION In the normal human exocervix, a greater density of ZIO-positive DCs was noted in the epithelium and subepithelium and their distribution was not uniform. In some areas of epithelium, the ZIO-positive cells in the basal layer showed a typical dendritic morphology, while the cells in the intermediate and superficial layers were nondendritic polygonal cells. Intraepithelial capillaries were noted, which were surrounded by ZIO-positive nondendritic polygonal cells. There was significant difference in the mean diameters of typical DCs (8.61±1.86 μm) and nondendritic polygonal cells (10.97±1.93 μm). In the subepithelium the DCs had typical morphology and their distribution varied. ZIO positive DCs were noted in the epithelium and cervical glands of endocervix also. In conclusion, the human cervix has different subsets of ZIO positive DCs with varied distribution. Their functional role has yet to be defined.

Morphology of Sigmoid Colon in South Indian Population: A Cadaveric Study

INTRODUCTION Sigmoid volvulus is a common etiological factor in acute large bowel obstruction. The increased length of sigmoid colon is attributed as one of the causes of sigmoid volvulus. AIM The aim of this study was to find the morphology of sigmoid colon in South Indian population using cadavers. MATERIALS AND METHODS The present study was performed with 31 cadavers used for teaching purpose. The sigmoid colon was classified into classical, long-narrow and long- broad types by their disposition in the abdominal cavity. The sigmoid loops relation to pelvic brim was also observed and grouped as pelvic and suprapelvic in position. The length of sigmoid colon along the mesenteric and antimesenteric border, height and width of sigmoid mesocolon in relation to the pelvic brim and the root of mesentery were measured in the study. RESULTS The study showed that the majority of the sigmoid colons fell into the classical type (47.6%). The sigmoid colon in pelvic position was significantly more prevalent. The mean length of sigmoid colon was 15.2 ± 4.4cm and 19.2 ± 6cm considering the pelvic brim and root of mesentery as reference points of measurement respectively. The mean length along antimesenteric border was 22.3 ± 7.9cm and 25 ± 8.7cm along the same reference points. The mean length of mesocolon height was 6.5 ± 3cm with reference to pelvic brim and 7.3 ± 3cm with reference to root of Sigmoid mesocolon respectively. The mean width of mesocolon was 7.4 ± 3cm (pelvic brim) and 8 ± 2cm (root of Sigmoid mesocolon) There was a positive correlation of sigmoid colon length with the height of the mesocolon. The gender analysis showed that males had statistically significant longer sigmoid colon and mesocolon. CONCLUSION This study documents that the South Indian population has a more classical type of sigmoid colon and that the anatomical dimensions of sigmoid colon and its mesocolon is significantly longer in males.