Scenario of ovarian mass lesions at a teaching hospital in Andhra Pradesh, India

Background: Ovary is the common site of non-neoplastic and neoplastic lesions which accounts for significant morbidity and mortality. The objective of present study was to ascertain the frequency and distribution of the various non-neoplastic and neoplastic ovarian mass lesions and to study the clinical and histopathological presentation.Methods: Observational study of cases with ovarian mass lesions subjected to surgical management from September 2009-August 2014 at our centre Government General Hospital/RMC Kakinada.Results: Incidence of ovarian masses was (n=404) 4.66% in 8,656 admissions subjected to surgical management. There were (340/404) 84.16% neoplasms and (64/404) 15.84% nonneoplastic lesions. Follicular and simple serous cysts were common non neoplastic lesions. Twisted ovarian cyst was the commonest surgical emergency. Age of the patients ranged from 9years to 82years.Mean ages of non-neoplastic, benign and malignant lesions were 34.2years, 36.8years and 44.7yrs.Most of the cases were in reproductive agegroup (p<0.001). Benign neoplasms were (248/340) 72.94%, borderline (26/340) 7.64% and malignant neoplasms were (66/340) 19.41%. Surface epithelial tumours dominated other types (78.12%) followed by germ cell tumours (12.05%) and sex cord stromal tumours (6.47%). Mucinous cystadenoma (34.11%) was the commonest benign tumour, followed by serouscystadenoma 23.53%. Commonest malignant ovarian tumour was serous cystadenocarcinoma (9.11%).Conclusion: Ovarian neoplasms were more common than non-neoplasms subjected to surgical management. Surface epithelial tumours were the commonest neoplasms with more benign neoplasms. Commonest benign neoplasm was mucinous cystadenoma and malignant was serous cystadenocarcinoma. Significant number of malignant ovarian tumors presented at an earlier age and in late stages

Imaging Mass Spectrometry Detection of Gangliosides Species Within the Mouse Brain Following Transient Focal Cerebral Ischemia

Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of ganglioside species using matrix-assisted laser desorption/ionization (MALDI) imaging (IMS) following middle cerebral artery occlusion (MCAO) reperfusion injury in the mouse. IMS is a powerful method to not only discriminate gangliosides by their oligosaccharide components, but also by their carbon length within their sphingosine base. Mice were subjected to a 30 min unilateral MCAO followed by long-term survival (up to 28 days of reperfusion). Brain sections were sprayed with the matrix 5-Chloro-2-mercaptobenzothiazole, scanned and analyzed for a series of ganglioside molecules using an Applied Biosystems 4800 MALDI TOF/TOF. Traditional histological and immunofluorescence techniques were performed to assess brain tissue damage and verification of the expression of gangliosides of interest. Results revealed a unique anatomical profile of GM1, GD1 and GT1b (d18∶1, d20∶1 as well as other members of the glycosphingolipid family). There was marked variability in the ratio of expression between ipsilateral and contralateral cortices for the various detected ganglioside species following MCAO-reperfusion injury. Most interestingly, MCAO resulted in the transient induction of both GM2 and GM3 signals within the ipsilateral hemisphere; at the border of the infarcted tissue. Taken together, the data suggest that brain region specific expression of gangliosides, particularly with respect to hydrocarbon length, may play a role in neuronal responses to injury

Imaging Mass Spectrometry Detection of Gangliosides Species in the Mouse Brain following Transient Focal Cerebral Ischemia and Long-Term Recovery

Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of ganglioside species using matrix-assisted laser desorption/ionization (MALDI) imaging (IMS) following middle cerebral artery occlusion (MCAO) reperfusion injury in the mouse. IMS is a powerful method to not only discriminate gangliosides by their oligosaccharide components, but also by their carbon length within their sphingosine base. Mice were subjected to a 30 min unilateral MCAO followed by long-term survival (up to 28 days of reperfusion). Brain sections were sprayed with the matrix 5-Chloro-2-mercaptobenzothiazole, scanned and analyzed for a series of ganglioside molecules using an Applied Biosystems 4800 MALDI TOF/TOF. Traditional histological and immunofluorescence techniques were performed to assess brain tissue damage and verification of the expression of gangliosides of interest. Results revealed a unique anatomical profile of GM1, GD1 and GT1b (d18∶1, d20∶1 as well as other members of the glycosphingolipid family). There was marked variability in the ratio of expression between ipsilateral and contralateral cortices for the various detected ganglioside species following MCAO-reperfusion injury. Most interestingly, MCAO resulted in the transient induction of both GM2 and GM3 signals within the ipsilateral hemisphere; at the border of the infarcted tissue. Taken together, the data suggest that brain region specific expression of gangliosides, particularly with respect to hydrocarbon length, may play a role in neuronal responses to injury

Transient and bilateral increase in Neuropilin-1, Fer kinase and collapsin response mediator proteins within membrane rafts following unilateral occlusion of the middle cerebral artery in mouse

Membrane rafts, rich in sphingolipids and cholesterol, are membrane microdomains important in neuronal domain-specific signaling events such as during axonal outgrowth and neuronal death. The present study seeks to determine the spatiotemporal association of several axonal guidance signaling molecules with membrane rafts. These molecules are Neuropilin-1 (NRP-1), Fer Kinase, and collapsin response mediator proteins (CRMPs), which are known to have important functions in axonal outgrowth and neuronal death caused by cerebral ischemia. Mice were subjected to sham or a 1 h unilateral middle cerebral artery occlusion (MCAO) followed by a time course of reperfusion up to 24 h. Brain cortices were separated and membrane rafts were extracted based on their insolubility in Triton X-100 and separation by sucrose gradient fractionation. We demonstrate the early and transient induction of NRP-1 and CRMP-2 in membrane rafts in both ipsilateral and contralateral hemispheres, in contrast to an early, but sustained elevation of Fer kinase and other CRMPs (1, 3, 4, 5) in response to unilateral MCAO. The fact that NRP1/Fer kinase/CRMP-2 co-localize in membrane rafts early during ischemic injury suggests that the membrane rafts may form a scaffold to support and initiate NRP1/Fer/CRMP-2-mediated signal transduction in neuronal damage response during ischemia-reperfusion. Further understanding of the time-specific and membrane domain-specific protein\u2013protein interaction may lead to the identification of therapeutic targets for stroke.Peer reviewed: YesNRC publication: Ye

Neuroregenerative strategies in the brain: emerging significance of bonemorphogenetic protein 7 (BMP7)

Every year thousands of people suffer from brain injuries and stroke, anddevelop motor, sensory, and cognitive problems as a result of neuronal loss in thebrain. Unfortunately, the damaged brain has a limited ability to enact repair andcurrent modes of treatment are not sufficient to offset the damage. An extensivelist of growth factors, neurotrophic factors, cytokines, and drugs has been exploredas potential therapies. However, only a limited number of them may actually have thepotential to effectively offset the brain injury or stroke-related problems. One ofthe treatments considered for future brain repair is bone morphogenetic protein 7(BMP7), a factor currently used in patients to treat non-neurological diseases. The clinical application of BMP7 is based on its neuroprotective role in stroke animal models. This paper reviews the current approac hes considered for brain repair and discusses the novel convergent strategies by which BMP7 potentially can induce neuroregenerationNRC publication: Ye

Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage

Semaphorin 3A (Sema3A) increased significantly in mouse brain following cerebral ischemia. However, the role of Sema3A in stroke brain remains unknown. Our aim was to determine wether Sema3A functions as a vascular permeability factor and contributes to ischemic brain damage. Recombinant Sema3A injected intradermally to mouse skin, or stereotactically into the cerebral cortex, caused dose-and time-dependent increases in vascular permeability, with a degree comparable to that caused by injection of a known vascular permeability factor vascular endothelial growth factor receptors (VEGF). Application of Sema3A to cultured endothelial cells caused disorganization of F-actin stress fibre bundles and increased endothelial monolayer permeability, confirming Sema3A as a permeability factor. Sema3A-mediated F-actin changes in endothelial cells were through binding to the neuropilin2/VEGFR1 receptor complex, which in turn directly activates Mical2, a F-actin modulator. Down-regulation of Mical2, using specific siRNA, alleviated Sema3A-induced F-actin disorganization, cellular morphology changes and endothelial permeability. Importantly, ablation of Sema3A expression, cerebrovascular permeability and brain damage were significantly reduced in response to transient middle cerebral artery occlusion (tMCAO) and in a mouse model of cerebral ischemia/haemorrhagic transformation. Together, these studies demonstrated that Sema3A is a key mediator of cerebrovascular permeability and contributes to brain damage caused by cerebral ischemia.Peer reviewed: YesNRC publication: Ye

Astrocyte-secreted GDNF and glutathione antioxidant system protect neurons against 6OHDA cytotoxicity

In recent years, GDNF has emerged as a protective and restorative agent in several models of neurodegeneration; however, the exact molecular mechanisms responsible for these effects are not yet fully understood. Here we examined the effects of astrocytes secreting GDNF on neurons subjected to 6OHDA toxicity using in vitro neuron-astroglia co-cultures. Astrocytes were transduced with lentiviral vectors carrying the GDNF gene under the control of either human glial fibrillary acidic protein or cytomegalovirus promoters. The overexpression of GDNF, regardless of the promoter employed, had no obvious adverse effects on astroglia and the engineered cells stably produced and secreted GDNF for extended periods of time ( 653 weeks). These astrocytes very effectively protected neurons against 6OHDA, in both mouse and human co-culture systems. The neuroprotective effects were mediated not only by GDNF, but also by the antioxidant GSH since its depletion reduced the level of GDNF protection. Furthermore, neurons and astrocytes expressed different components of GDNF signaling complex, suggesting that they might utilize separate pathways to mediate autocrine and paracrine effects of GDNF.Peer reviewed: YesNRC publication: Ye

GM1 imaging within a mouse brain following a unilateral MCAO and long-term survival.

<p>Mice received a 30 min unilateral MCAO followed by reperfusion time points of 24 h, 3 d, 7 d, 14 d and 28 d. Adjacent sections were either stained with Cresyl violet; or were scanned using mass spectrometry imaging. Mass spectrometry images for each time point were from the same coronal tissue section. Both GM1 d18∶1 (m/z 1546) and d20∶1 (m/z 1574) were expressed at higher levels within the MCAO-induced infarcted hemisphere, specifically within the cerebral cortex, hippocampus and striatum.</p

Summary of ganglioside expression with respect to ROIs.

<p>The mean intensities of ganglioside derived from the mass spectra were expressed as fold increases/decreases between ipsilateral and contralateral ROIs. Each paired bar represents the d18∶1 (black-colored bar) and d20∶1 (red-colored bar) moieties for each ganglioside species detected. Bars within the box represent the time course (sham, 24 h, 3 d, 7 d, 14 d and 28 d) following MCAO for each ganglioside (GM3, GM3, GM1, GD1 and GT1b).</p