Ellagic acid ameliorates cisplatin induced hepatotoxicity in colon carcinogenesis

The clinical application of cisplatin (CP), one of the most extensively used antineoplastic drug, is restricted by its numerous side effects. CP's antitumor potential resides in the free generation of reactive oxygen species leading to oxidative stress. This stress is a source of the side effects associated with its use. Ellagic acid (EA), a polyphenol is known to possess multiple health benefits owing to its antioxidant properties. EA is largely metabolized by the colon microbiota of different mammals and therefore was a polyphenol of choice in the present study. The present study was thus carried out to explore the protective potential of EA on CP induced hepatotoxicity in colon tumor bearing mice. The administration of EA (10 mg/kg bwt po daily for 6 weeks) significantly ameliorated the toxicity caused by CP (5 mg/kg bwt ip once a week for 4 weeks). Activities of liver marker enzymes and lactate dehydrogenase were brought back to normal. EA cotreatment also led to a marked reduction in the extent of peroxidative damage to liver tissue as was evident from the improvement in the histopathological changes observed and FT‐IR analysis. The present study, therefore, suggests that the administration of EA reduces the CP‐induced hepatotoxicity, thereby emerging out as a potential candidate for chemopreventive action.     

Membranous nephropathy with light chain restricted deposits

The literature on membranous nephropathy (MN) with monoclonal deposits on immunofluorescence (IF) and their outcome is very scarce. We report our experience of managing five patients with this clinical entity. The mean age of the patients was 33.2 ± 6.55 years. The mean proteinuria, serum albumin and serum creatinine was 5.73 ± 2.17 g/day, 2.86 ± 0.51 g/dL and 1.34 ± 1.19 mg/dL, respectively. None of the patients had a lymphoproliferative disorder. Only one patient had an elevated free light chain ratio. Four (80%) patients were M‐type phospholipase A2 receptor (PLA2R) negative (tissue and serum), and one (20%) was PLA2R related. Three (60%) cases had monoclonal IgG3/k, one IgG3/λ, whereas one patient with PLA2R positivity had an IgG3/IgG4k subtype. Two (67%) patients treated with cyclical cyclophosphamide and steroids (cCYC/GC) achieved complete remission and one patient (33%) with elevated baseline creatinine had a reduction in serum creatinine with persistent proteinuria at the end of the 12th month of follow‐up. One patient with PLA2R positive MN was treated with Rituximab and is in complete remission. The patient with an elevated free light chain at baseline was treated with Bortezomib/Thalidomide/Dexamethasone, had complete remission at 12 months, however, had a progressive rise in creatinine over the next 40 months of follow‐up. The current series, though limited by numbers, documents the efficacy of conventional therapies in non‐malignant associated MN with monoclonal deposits on IF.     

On the Role of Ultrasonography and CT Scan in the Diagnosis of Acute Appendicitis

The purposes of this study were to revisit the utility of ultrasonography (USG) as a primary imaging modality in acute appendicitis (AA) and to establish the role of CT scan as a second-line/problem-solving modality. All cases of suspected AA were referred for urgent USG. USG was done with standard protocol for appendicitis. Limited computed tomographic (CT) scan [NCCT ± CECT (IV contrast only)] was done for the lower abdomen and pelvis where sonographic findings were equivocal. One hundred and twenty-one patients were referred for USG for suspected appendicitis. Eight-four patients underwent surgery for AA based on clinical as well as imaging findings, of whom 76 had appendicitis confirmed at histopathology. Three patients were misdiagnosed (3.6 %) on USG as appendicitis. Of 76 patients of appendicitis confirmed histopathologically, 63 (82.8 %) had features of appendicitis on USG and did not require any additional imaging modality. Of 121 patients, 12 (10 %) needed CT scan because of atypical features on USG. Of these 12 patients, seven had retrocecal appendicitis, and three high-up paracolic appendicitis. USG alone had sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 81, 88, 92.6, 71.6, and 83 %, respectively. When combined with CT scan in select cases, the sensitivity, specificity, PPV, NPV, and accuracy of combined USG + CT scan were 96 % (P?=?0.0014), 89 %, 93 %, 93.5 % (P?=?0.0001), and 93 % (P?=?0.0484), respectively. Twenty-eight (23 %) patients were given alternative diagnosis on USG. Dedicated appendiceal USG should be used as a primary imaging modality in diagnosing or excluding AA. Appendiceal CT can serve as a problem-solving modality.     

Sentinel Lymph Node Localization Using 1 % Isosulfan Blue Dye in Cases of Early Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

To study the use of 1 % isosulfan blue dye in identifying sentinel node, sensitivity and specificity of frozen section and predictive value of sentinel node in predicting other nodal status in the cases of oral cavity and oropharyngeal squamous cell carcinoma. 15 patients of oral cavity and oropharyngeal SCC with clinically N0 neck, who required WLE of the primary lesion as well as neck dissection as per recommended treatment protocol, were selected from OPD. 1 % Isosulfan dye was injected peritumorally intraoperatively after the induction of general anaesthesia. Neck dissection was performed and first node taking up the blue dye was identified, dissected, removed and was sent for frozen section. In two of the 15 cases a sentinel node was identified (sensitivity of the technique—13 %). Both the sentinel nodes were positive for presence of metastasis on final histopathology (specificity—100 %). However, five cases had nodal metastasis on final histopathological examination of the neck dissection specimen (sensitivity of sentinel lymph node biopsy—40 %). Frozen section examination had a sensitivity and specificity of 100 %. All data was analyzed using SPSS 16 software. Use of 1 % Isosulfan Dye for identification of sentinel node is a simple and cheap technique, however, it has low sensitivity as compared to the use of triple diagnostic procedure consisting of lymphoscintigraphy, per op gamma probe localization and using isosulfan dye for sentinel node identification. Sentinel lymph node is representative of nodal status and correlates well with the final histopathological examination of the dissected neck nodes.     

Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation

This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue‐Periodic Acid Schiff (AB‐PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 999–1013, 2015.     

Ethanol and Vitamin D Receptor in T Cell Apoptosis

Ethanol has been demonstrated to cause T cell apoptosis. In the present study, we evaluated the role of VDR and the renin angiotensin system (RAS) in oxidative stress-induced T cell apoptosis. Ethanol-treated human T cells displayed down regulation of vitamin D receptor (VDR) and the activation of the RAS in the form of enhanced T cell renin expression and angiotensin II (Ang II) production. The silencing of VDR with siRNA displayed the activation of the RAS, and activation of the VDR resulted in the down regulation of the RAS. It suggested that ethanol-induced T cell RAS activation was dependent on the VDR status. T cell ROS generation by ethanol was found to be dose dependent. Conversely, ethanol-induced ROS generation was inhibited if VDR was activated or Ang II was blocked by an angiotensin II type 1 (AT1) receptor blocker (Losartan). Furthermore, it was observed that ethanol not only induced double strand breaks in T cells but also attenuated DNA repair response, whereas, VDR activation inhibited ethanol-induced double strand breaks and also enhanced DNA repairs. Since free radical scavengers inhibited ethanol-induced DNA damage, it would indicate that ethanol-induced DNA damage was mediated through ROS generation. These findings indicated that ethanol-induced T cell apoptosis was mediated through ROS generation in response to ethanol-induced down regulation of VDR and associated activation of the RAS.