Topical Dexamethasone Counters Intravitreal Ivermectin-Induced Ocular Toxicity in a Rabbit Model.

PURPOSE: Systemic use of Ivermectin has been reported to incite blindness in humans and veterinary patients. This study was designed to investigate the systemic and intravitreal effect of Ivermectin on ocular and retinal health and its attenuation with topical Dexamethasone. METHODS: Systemic injection of Ivermectin@ 1.6 mg/kg S/C was administered, thrice a week for three weeks to New Zealand White rabbits (N = 4) with and without topical drops of Verapamil (N = 4). Pre and post-treatment ocular examination was conducted. At the end of three weeks the eyes were collected for histopathology.0.2 ml of Ivermectin solution (1.6 mg/ml) was injected intravitreally in one eye of the rabbit (N = 8), Half the rabbits received 0.1% dexamethasone drops thrice daily for 7 days, while the controls received PBS. Pre and post-treatment, detailed examination was conducted, which included the Schirmer Tear test, Fluorescein staining, Intraocular pressure, slit lamp biomicroscopy and fundus photography. The retina was harvested for histopathological and tunnel assay. RESULTS: Systemic therapy with Ivermectin, with and without Verapamil did not incite any adverse response in the eye. Intravitreal Ivermectin evoked severe uveitis 4/4, cataract 3/4, corneal erosion 3/4 eyes and severe inflammatory response. Eyes that received dexamethasone were rescued from the adverse changes as demonstrated clinically, by histopathology and prevention of apoptosis. CONCLUSIONS: Intravitreal Ivermectin incites severe inflammatory response. Topical dexamethasone counters the ocular toxicity incited by Ivermectin.

Spectrum of pediatric kidney tumours with special references to WT1 immunostain at a tertiary care hospital.

Context or Background: Pediatric renal tumours are the second most common solid tumours in children. The most common in this group is Wilms tumour with mesoblastic nephroma being the 2nd most common tumour in children, younger than 3 months. Aims and Objectives: The present study was conducted to study the epidemiological occurrence of pediatric renal tumours at a tertiary care hospital and to study the diagnostic efficacy of WT1 immunostaining in distinguishing Wilms tumour from other types of renal tumours. Materials and Methods: It was a single institution-based prospective and observational study conducted for 2 years (from October 2013 to September 2015) in the department of pathology in our hospital. A total of 50 cases were enrolled in this study all were below 15 years of age. Results: Nephroblastoma or Wilms tumour was found to be the most common type, occurring in 66% cases. Fourteen out of 33 cases of Wilms tumour showed triphasic components (blastemal, epithelial, and stromal) with Blastemal type Wilms being the second most common (11 cases). WT1 immunostaining was positive in 93.9% cases of nephroblastoma. The highest amount of nuclear positivity noted in blastemal cells followed by epithelial cells. Rhabdomyoblastic differentiation and regressive variant showed nonspecific cytoplasmic staining. Cystic partially differentiated nephroblastoma and diffuse anaplasia type Wilms tumour showed nuclear staining in blastemal cells. Conclusion: The expression of WT1 immunostain was found to be diagnostically significant in differentiating Wilms tumour from other renal tumours.

Lymph node characteristics and their prognostic significance in oral squamous cell carcinoma.

BACKGROUND: The prognostic significance of various histopathologic lymph node-based biomarkers in oral squamous cell carcinoma (OSCC) needs further evaluation. METHODS: Retrospective analysis of 212 OSCC patients with regional metastasis to determine the association of extranodal extension (ENE), extent of ENE, size of metastatic deposit, lymph node yield (LNY), lymph node ratio (LNR), and topography of involvement with survival outcomes. RESULTS: The presence of ENE, larger nodal deposit, higher pN stage, lymph nodes in the lower levels, and patients who did not receive adjuvant treatment had poor disease-free survival (DFS). In addition, more positive nodes and high LNR showed worse overall survival (OS). ENE beyond 5 mm resulted in poorer outcomes. Larger sizes of metastatic deposit predisposed to ENE. Multivariate analyses showed only lower level of neck involvement to affect both DFS and OS. CONCLUSIONS: Lymph node metastasis to lower levels and other lymph node characteristics affect prognosis and must be considered in the evolution of staging systems for OSCC.

Mitigating fibrosis-An impediment to corneal re-innervation following lamellar flap surgery.

Restoration of corneal sensitivity is of utmost importance to maintain corneal homeostasis following any injury or insult, for which, both corneal nerve regeneration and re-innervation are essential. Fibrosis poses a major impediment for re-innervation. We have in this study evaluated the influence of various nerve growth factors and corneal fibrosis on corneal nerve regeneration and reinnervation following lamellar flap surgery (LFS) and its modulation using antifibrotic drug pirfenidone. To achieve this, trigeminal ganglion cells were treated with pirfenidone, NGF, and NT-3 to evaluate their effect on trigeminal cell neurite growth. Following LFS, the gene expression of nerve growth factors NGF, BDNF and NT-3, Gap 43, Nogo-A and profibrotic factors Tenascin C, TGF-beta 1 were evaluated with and without pirfenidone. Wound fibrosis and corneal nerve regeneration using pirfenidone following LFS were evaluated by staining whole corneal mounts with α SMA and ß tubulin 3. Safety of NGF and pirfenidone topical drops in normal unoperated cornea and its efficacy in enhancing corneal healing was evaluated following LFS. Our study shows, pirfenidone did not influence trigeminal cell neurite elongation; NGF and NT-3 significantly enhanced trigeminal cell neurite elongation. NT-3 also significantly increased neurite branching. There was significant increase in the gene expression of NGF, BDNF, NT-3, Gap- 43, TGF beta-1, Tenascin C, Nogo-A genes in the operated cornea compared to normal cornea, treatment of operated corneas with pirfenidone prevented the increased expression of these genes except Gap 43 which remained unchanged. The treatment of operated eyes with combination of NGF and pirfenidone positively influenced corneal healing compared to treatment with NGF alone, and had no adverse influence on the cornea. Pirfenidone appreciably reduced corneal fibrosis which aided in re-innervation. Both NGF and NT3 positively influence trigeminal neurite elongation. NGF and pirfenidone have complementary influence on corneal wound healing.

Bis (Isothiocyanatomethyl) Benzene, A Plant Derived Anti-Neoplastic Compound: Purified from Moringa Oleifera Leaf Extract.

BACKGROUND: Moringa oleifera lam, commonly known as "Sajina", is an indigenous species to India. In our folk medicine, it is used for the treatment of Canker (cancer). The Moringa oleifera leaf extract contains many phyto-compounds, with some being anti-neoplastic in nature. OBJECTIVE: Our preliminary study showed that the leaf extract significantly kills cancer cells compared to normal cells. On searching for the new phyto-compound, Bis-isothiocyanatomethyl) benzene was purified and isolated. METHODS: The sequential process of fractional distillation, column chromatography, followed by TLC and HPLC is performed for purification. Every fraction from each step was tested on HeLa cell line for evaluating the presence of the phyto-compound. RESULTS AND CONCLUSION: FTIR peak analysis of a single phyto-compound shows the presence of thiocyanate group, aromatic carbon group. 1H & 13C NMR peak analysis along with High-resolution mass spectroscopy (HRMS) calculation confirm the chemical structure with IUPAC name [Bis (Isothiocyanatomethyl) benzene]. Previously, Isothiocyanatomethyl- benzene solely or in conjugation with sugar molecule has been reported, but its dimeric form in nature hasnot yet been published anywhere. It shows anticancer activity by retarding cancer cell growth & inhibits carcinogenesis on HeLa, MCF-7, and MDA-MB-231 cell lines by caspase 3 apoptotic pathway and showed comparatively less cytotoxicity to PBMC cell. It shows anticancer activity almost the same as the market available drug Cis-Platin. Therefore, further extrapolating its activity with different concentrations may result in its use as a drug formulation for the treatment of cancer.

Evaluation of diagnostic utility of imprint cytology in paediatric renal tumours with special references to Ki 67 proliferative marker.

BACKGROUND: Pediatric renal neoplasms comprise about 7%-8% of all neoplasms in children. Wilms tumour (WT) is the most common among pediatric renal tumours. AIMS AND OBJECTIVES: The study was undertaken to study the epidemiological occurrence of pediatric renal tumours in a tertiary care hospital and to ascertain the validity and reliability of touch smear imprint cytology in intraoperative diagnosis of renal tumours and correlate with subsequent histopathological diagnosis and to assess the expression of proliferation marker Ki-67 in different components and stages of WT. MATERIALS AND METHODS: It was a single-institution-based prospective and observational study, conducted for 2 years (from October 2013 to September 2015) in the department of pathology at our hospital. A total of fifty cases were enrolled in this study, all were below 15 years of age. RESULTS: Imprint cytology showed sensitivity, specificity, and diagnostic accuracy of 83%, 98%, and 95.74%, respectively, in diagnosing benign and malignant renal tumours. There was statistically significant correlation of imprint cytology with confirmatory histopathological examination of excision specimen (P < 0.001). Immunohistochemical analysis of Ki-67 was done in all WT cases. Epithelial component had higher proliferative index than blastemal component with P = 0.0082, which was highly statistically significant. CONCLUSION: Imprint cytology is found to be a less expensive, simple, and rapid method, which can be used as an adjunct to histopathology. Correlation between proliferation index as measured with Ki-67 antibody and tumour stage was found. Ki-67 is thus a relevant marker for assessing the proliferative activity.

Soft-tissue amyloidoma with associated plasmacytoma.

Soft tissue amyloidoma with features similar to plasmacytoma, in absence of systemic amyloidosis, is an extremely rare finding. We hereby report the case of a 77 year old man who presented with a painless, nodular swelling on chest wall, diagnosed as soft tissue amyloidoma with plasma cell infiltration. Congo red staining was done to prove the presence of amyloid which showed characteristic "apple-green" birefringence on polarized microscopy. The plasma cells were monoclonal in origin as demonstrated by serum protein and immunofixation electrophoresis. To the best of our knowledge, this is the second such reported case. However close follow up is required, as this patient may develop multiple myeloma in future.