Rat BM-MSCs secretome alone and in combination with stiripentol and ISRIB, ameliorated microglial activation and apoptosis in experimental stroke.

BACKGROUND: Stroke, a devastating neurological emergency, is the leading cause of worldwide mortality and functional disability. Combining novel neuroprotective drugs offers a way to improve the stroke intervention outcomes. In the present era, the combination therapy has been proposed as a plausible strategy to target multiple mechanisms and enhance the treatment efficacy to rescue stroke induced behavioral abnormalities and neuropathological damage. In the current study, we have investigated the neuroprotective effect of stiripentol (STP) and trans integrated stress response inhibitor (ISRIB) alone and in combination with rat bone marrow derived mesenchymal stem cells (BM-MSCs) secretome in an experimental model of stroke. MATERIALS & METHODS: Stroke was induced in male Wistar rats (n = 92) by temporary middle cerebral artery occlusion (MCAO). Three investigational agents were selected including STP (350 mg/kg; i.p.), trans ISRIB (2.5 mg/kg; i.p.) and rat BM-MSCs secretome (100 µg/kg; i.v). Treatment was administered at 3 hrs post MCAO, in four doses with a 12 hrs inter-dose interval. Post MCAO, neurological deficits, brain infarct, brain edema, BBB permeability, motor functional and memory deficits were assessed. Molecular parameters: oxidative stress, pro inflammatory cytokines, synaptic protein markers, apoptotic protein markers and histopathological damage were assessed. RESULTS: STP and trans ISRIB, alone and in combination with rat BM-MSCs secretome, significantly improved neurological, motor function and memory deficits along with significant reduction in pyknotic neurons in the brain of post MCAO rats. These results were correlating with significant reduction in pro-inflammatory cytokines, microglial activation and apoptotic markers in the brain of drug treated post MCAO rats. CONCLUSION: STP and trans ISRIB, alone and in combination with rat BM-MSCs secretome, might be considered as potential neuroprotective agents in the acute ischemic stroke (AIS) management.

Predisposing factors and histopathological variants of cutaneous squamous cell carcinoma: Experience from a North Indian teaching hospital.

BACKGROUND: Squamous and basal cell carcinomas together constitute the majority of non-melanoma skin cancers. These malignancies are infrequent in Indians as compared to the white skinned population. Literature on squamous cell carcinoma in dark skin is limited. AIM: To analyze the risk factors and to characterize the histopathological subtypes of cutaneous squamous cell carcinoma in Indian patients in an area, non-endemic for arsenicosis. METHODS: A retrospective analysis of data from January 2003 to August 2013 was performed to evaluate the predisposing factors and histopathological types of cutaneous squamous cell carcinoma at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh. Demographic and disease characteristics such as age, gender and predisposing factors, particularly premalignant dermatoses were recorded and histopathology slides were reviewed. RESULTS: Of the 13,426 skin biopsy specimens received during the 10-year period, there were 82 (0.6%) cases of squamous cell carcinoma and 170 (1.7%) of basal cell carcinoma. The mean age at diagnosis of cutaneous squamous cell carcinoma was 53.7 years and the male to female ratio was 2:1. The most common site of involvement was the lower limbs in 34 (41.5%) patients. Marjolin's ulcer was present in 36 (43.9%) cases. No predisposing factor was identified in 35 (42.7%) patients. Histopathologically, the tumors were classified most commonly as squamous cell carcinoma not otherwise specified in 33 (40.2%) cases. LIMITATIONS: This was a retrospective study and details of occupation and interval between the precursor lesions and development of tumor were not recorded. Immunohistochemistry for human papilloma virus and p53 tumor suppressor protein were not performed as these tests were not available. CONCLUSION: Cutaneous squamous cell carcinoma is uncommon in Indian patients and a high index of suspicion is necessary when a rapidly enlarging nodule, verrucous fungating plaque or an ulcer with everted margins develops in long standing scars and other predisposing dermatologic conditions. Histopathological examination is mandatory to confirm the diagnosis and identify the subtype and this has prognostic implications.

Primary calvarial Ewing's sarcoma presenting as a giant fungating skull tumour: a case report.

Giant calvarial Ewing's sarcoma is a rare entity. A 9-year-old girl presented with such a lesion, larger than her head and was fungating through the overlying skin. Surgical excision was done and the child was given chemotherapy. The child died after the second cycle. It is extremely uncommon to come across this disease in such an advanced stage.

Duodenojejunal intussusception in Peutz-Jeghers syndrome: Report of a case.

Recurrent intussusception is one of the common modes of presentation in patients with Peutz-Jeghers syndrome. This report presents a case of Peutz-Jeghers syndrome with synchronous duodenojejunal and jejunojejunal intussusceptions due to hamartomatous polyps. Very few cases of duodenojejunal intussusception in Peutz-Jeghers syndrome patients have so far been reported in the literature.

MIB-1 immunolabeling: a valuable marker in prediction of benign recurring meningiomas.

Histological analysis has limited value to predict biological behavior of meningiomas. We investigated the utility of cell proliferative indicator in the evaluation of histologically benign meningiomas. We selected 25 benign non-recurrent meningiomas, 15 benign recurrent meningiomas after complete surgical resection, 30 atypical meningiomas, and 15 anaplastic meningiomas out of 384 cases studied. MIB-1 Labeling Index was evaluated by two methods: Highest Labeling Index (HLI) and Random Labeling Index (RLI). There was no dependable histological parameter to predict recurrence among benign-looking meningiomas. HLI had significant difference when compared with RLI in all categories. The mean MIB-1 HLI values +/- SD were 3.47 +/- 2.0% for benign meningiomas, 5.08 +/- 4.0% for atypical meningiomas and 11.66 +/- 7.06% for anaplastic meningiomas. In comparison, the mean MIB-1 HLI of benign non-recurrent meningiomas were 2.66 +/- 1.7% and with recurrence were 4.21 +/- 2.78% (P = 0.0339). Using receiver operating characteristic, it was seen that neoplasm recurred with the MIB-1 HLI of > 2.6 having the sensitivity of 64.6% and specificity of 68% among benign (grade I) meningiomas. MIB-1 positive tumor cells were maximally aggregated at the periphery of excised specimen. MIB-1 HLI, integrated with standard histopathology can provide better information about the disease biological nature in benign meningiomas.

Does c-erbB-2 expression have a role in medulloblastoma prognosis?

The prognosis of patients with medulloblastoma has remained same for the last two decades. This study evaluated the role of c-erbB-2 expression in medulloblastoma as a prognostic marker. Fifty cases of medulloblastomas were investigated for the expression of c-erbB-2 protein using immunohistochemistry. The expression of c-erbB-2 was correlated with age, histology and disease-free survival (DFS). Thirty-five (70%) tumors were c-erbB-2 positive. Immunoreactivity for c-erbB-2 receptor was observed as mixed cytoplasmic and membrane positivity of tumour cells. The mean DFS in c-erbB-2 positive cases was 19.81 months compared to 48.33 months in c-erbB-2 negative cases. c-erbB-2 positivity was found to be an independent predictor of poor outcome in medulloblastoma (p value < 0.05). No correlation of c-erbB-2 expression was observed with the age of patient and the histological type of tumour. Additionally, c-erbB-4 expression was also evaluated in these tumours. Thirty-three cases showed co-expression of c-erbB-2 and c-erbB-4 proteins. However, c-erbB-4 expression alone was not associated with poor outcome, whereas its co-expression with c-erbB-2 was associated with shorter DFS (p < 0.05).

Primary hyperparathyroidism in north India: a description of 52 cases.

BACKGROUND: Primary hyperparathyroidism (PHPT) has a variable clinical expression. Symptomatic PHPT is still the predominant form of the disease in many parts of the world, especially developing countries. Because the clinical profile of the disease has changed from that described in the past, we sought to improve our understanding of the disease in patients in north India. METHODS: We summarized the clinical presentation, biochemical and radiological features, and operative findings from the case records from the last 13 years of 52 patients at a tertiary care centre in north India who had documented PHPT. RESULTS: The male: female ratio was 1: 3.3 with ages ranging from 6 to 60 years (mean +/- SD, 36.38 +/- 12.73). Bone disease (46%), recurrent renal stones (21%) and body aches and pains (21%) were the most common modes of presentation. The lag time varied ranged from 1 month to 16 years. Common clinical manifestations included bone pain (67%), weakness/fatigue (56%), fracture of the long bones (48%), abdominal pain (39%), polyuria (37%) and psychiatric manifestations (23.1%). Hypertension was observed in 42% and a palpable nodule in the neck in 19%. Biochemical features included hypercalcemia (86.5%), hypophosphatemia (65.4%) and hyperphosphatasia (67.3%). Mean intact PTH ( +/- SD) was 809.0 +/- 696.3 ng/L with levels significantly lower in patients who had only kidney stone disease as compared with those with bone disease (P = 0.017). A single parathyroid adenoma was localized in 50 (98%) patients. Hungry bone disease was seen in 59% patients. CONCLUSION: PHPT in India continues to be a symptomatic disorder with skeletal and renal manifestations at a much younger age.

Morphometric image analysis of follicular lesions of the thyroid.

OBJECTIVE: To determine the role of image morphometry in distinguishing various follicular lesions of the thyroid in cytologic smears. STUDY DESIGN: Archival fine needle aspiration smears of 10 cases each of follicular hyperplasia, follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma were used for the study. All cases were histopathologically proven. At least 100 random nuclei from each case were subjected to analysis with an image cytometer. Area, convex area, length, width, perimeter, convex perimeter and roundness of nuclei were measured using a 40 x objective (1 pixel = 0.446 micron). RESULTS: ANOVA showed that all the nuclear variables studied were significantly different (P < .05) in follicular hyperplasia as compared to follicular carcinoma and papillary carcinoma. All nuclear variables except roundness were also significantly different (P < .05) between follicular hyperplasia and follicular adenoma. However, between follicular adenoma, follicular carcinoma and papillary carcinoma there was considerable overlap of nuclear morphometric parameters. CONCLUSION: Image morphometry may help to distinguish nonneoplastic follicular lesions (hyperplasia) from neoplastic lesions (adenomas and carcinomas). However, to distinguish benign from malignant follicular lesions, image morphometry might not improve the accuracy of standard cytologic examination.