Supplementation of Spirulina (Arthrospira platensis) Improves Lifespan and Locomotor Activity in Paraquat-Sensitive DJ-1ßΔ93 Flies, a Parkinson's Disease Model in Drosophila melanogaster.

Spirulina (Arthrospira platensis) is a cyanobacterium (blue-green alga) consumed by humans and other animals because of its nutritional values and pharmacological properties. Apart from high protein contents, it also contains high levels of antioxidant and anti-inflammatory compounds, such as carotenoids, ß-carotene, phycocyanin, and phycocyanobilin, indicating its possible pharmaco-therapeutic utility. In the present study using DJ-1ßΔ93 flies, a Parkinson's disease model in Drosophila, we have demonstrated the therapeutic effect of spirulina and its active component C-phycocyanin (C-PC) in the improvement of lifespan and locomotor behavior. Our findings indicate that dietary supplementation of spirulina significantly improves the lifespan and locomotor activity of paraquat-fed DJ-1ßΔ93 flies. Furthermore, supplementation of spirulina and C-PC individually and independently reduced the cellular stress marked by deregulating the expression of heat shock protein 70 and Jun-N-terminal kinase signaling in DJ-1ßΔ93 flies. A significant decrease in superoxide dismutase and catalase activities in spirulina-fed DJ-1ßΔ93 flies tends to indicate the involvement of antioxidant properties associated with spirulina in the modulation of stress-induced signaling and improvement in lifespan and locomotor activity in Drosophila DJ-1ßΔ93 flies. Our results suggest that antioxidant boosting properties of spirulina can be used as a nutritional supplement for improving the lifespan and locomotor behavior in Parkinson's disease.

In Vivo Efficacy of Latex from Calotropis procera in Ameliorating Fever-Biochemical Characteristics and Plausible Mechanism.

Calotropis procera latex fractions possessing anti-inflammatory property were characterized for their biochemical properties, compared for their efficacy in ameliorating fever in rats and their mechanism of action was elucidated. Aqueous fraction and methanol extract (AqDL and MeDL) were derived from the dried latex (DL) and proteins were separated from the fresh latex (LP). Polyacrylamide gel electrophoresis carried out under denaturing conditions showed the presence of proteins with some similarity in LP and AqDL and both of these fractions exhibited proteinase activity by gelatin zymography. A further analysis revealed that only the LP fraction possesses cysteine proteinase activity. Oral administration of both AqDL and MeDL produced a dose-dependent reduction in body temperature in rats where fever was induced by yeast and their effect was comparable to that of standard drug paracetamol while intravenous administration of LP was not so effective. Both AqDL and MeDL produced a significant reduction in the levels of TNF-α, PGE2, and immunoreactivity of COX-2 in the hypothalamus as compared to yeast control group. This study shows that both AqDL and MeDL, the orally effective anti-inflammatory fractions of latex, have therapeutic potential in treating various febrile conditions.

Cerebral gliosarcoma: Analysis of 16 patients and review of literature.

BACKGROUND: Gliosarcoma (GS), a subtype of glioblastoma (GBM), is a rare primary neoplasm of the central nervous system. Certain features like temporal lobe affinity, tendency for extraneural metastasis and poorer outcome compared to GBM indicate that GS may indeed be a separate clinicopathologic entity. This led us to revisit this entity in our settings. MATERIALS AND METHODS: Between 2009 and 2014, 16 cases of histologically proven GSs (14 primary, two secondary) were treated. Patient data were retrieved retrospectively. Statistical analysis was performed with? Statistical Package for Social Sciences, version 17.0. (Chicago, Illinois, USA). Survival was analyzed by Kaplan-Meier method. RESULTS: GS predominantly affected males in their fifth decade of life. Raised intracranial pressure was the most common mode of clinical presentation. Temporal lobe was the most commonly affected part of the brain and majority of primary and all of secondary GBM were located peripherally. In 7 (43.8%) patients, tumor was radiologically well-demarcated and enhanced strongly and homogenously on contrast as compared to 9 (56.2%) patients where the tumor was ill-defined and showed heterogenous patchy or ring enhancement. Extent of excision was total in seven patients (43.8%), near total in 4 (25%) and subtotal in five patients (31.2%). Median survival was 6 months. Patients with well-demarcated, enhancing mass on imaging intraoperatively had firm tumors with a good plane of cleavage and had a better survival (8 months) compared to those in whom the tumor radiologically and intraoperatively mimicked GBM (2 months). CONCLUSION: GS is associated with poor survival (median survival 6 months). Radiological and intraoperative findings help categorize these tumors into GBM like GS and meningioma like GS. While the former histologically mimics GBM and has very poor survival (2 months), GS with meningioma like feature tends to have better survival (8 months).

Protective effect of proteins derived from Calotropis procera latex against acute inflammation in rat.

The non-dialysable proteins present in the latex of plant Calotropis procera possess anti-inflammatory and analgesic properties. The aim of this study was to evaluate the effect of latex proteins (LP) on the level of inflammatory mediators, oxidative stress markers and tissue histology in the rat model of carrageenan-induced acute inflammation. This study also aimed at evaluating the anti-inflammatory efficacy of LP against different mediators and comparing it with their respective antagonists. Paw inflammation was induced by subplantar injection of carrageenan, and the effect of LP was evaluated on oedema volume, level of TNF-α, PGE(2), myeloperoxidase, nitric oxide, reduced glutathione, thiobarbituric acid-reactive substances and tissue histology at the time of peak inflammation. Paw inflammation was also induced by histamine, serotonin, bradykinin and PGE(2), and the inhibitory effect of LP against these mediators was compared with their respective antagonists at the time of peak effect. Treatment with LP produced a dose-dependent inhibition of oedema formation, and its anti-inflammatory effect against carrageenan-induced paw inflammation was accompanied by reduction in the levels of inflammatory mediators, oxidative stress markers and normalization of tissue architecture. LP also produced a dose-dependent inhibition of oedema formation induced by different inflammatory mediators, and its efficacy was comparable to their respective antagonists and more pronounced than that of diclofenac. Thus, our study shows that LP has a potential to be used for the treatment of various inflammatory conditions where the role of these mediators is well established.

Artesunate Ameliorates Functional Limitations in Freund's Complete Adjuvant-Induced Monoarthritis in Rat by Maintaining Oxidative Homeostasis and Inhibiting COX-2 Expression.

Drugs exhibiting anti-inflammatory and analgesic properties have been clinically used in the management of pain and impairment of joint functions in arthritis. In view of available studies on the beneficial effect of artesunate in various inflammatory conditions, the present study was carried out to evaluate its efficacy in ameliorating functional limitations of arthritis and to understand the underlying mechanisms. The study was carried out in rat model of Freund's complete adjuvant-induced monoarthritis where artesunate was found to produce a dose-dependent reduction in joint inflammation, improvement in functional parameters like stair climbing ability, motility, and suppression of mechanical allodynia at the doses of 50 and 150 mg/kg. Our study shows that protection afforded by artesunate was brought about by decreasing the levels of nitric oxide, influx of neutrophils, maintenance of oxidative homeostasis, inhibition of COX-2 expression, and apoptosis. Further, histological analysis of the arthritic joints also substantiated the anti-inflammatory property of artesunate. Thus, our study shows that artesunate has a potential for use in the treatment of arthritis.

Influence of DMF-induced oxidative stress on membrane and periplasmic proteins in Paracoccus sp. SKG.

The present study describes the N,N-dimethylformamide (DMF)-induced oxidative stress in Paracoccus sp. SKG. The oxidative stress was evaluated by analysing membrane and periplasmic proteins and K+ efflux, as well as by monitoring the activities of antioxidant enzymes like catalase, superoxide dismutase (SOD) and glutathione S-transferase (GST). The exposure of bacterial cells to a higher concentration of DMF resulted in the modification of membrane fatty acid composition which is accompanied by K+ efflux. Further, this oxidative stress resulted in increased periplasmic protein which can be attributed to the induction of GST and methionine sulphoxide reductase (Msr) enzymes under solvent stress. Paracoccus sp. SKG is tolerant to high concentrations of DMF up to 6% (v/v) and its toxic effects. DMF concentration-dependent induction of GST and Msr activities advocates the significant role of these enzymes in the bacterial defence system. The present study provides information which helps us to understand the ROS scavenging machinery in bacteria. The high tolerance of Paracoccus sp. SKG to DMF can be efficiently explored for various bioremediation and biotransformation applications.

Risk of hepatitis B infection in pediatric acute lymphoblastic leukemia in a tertiary care center from South India.

BACKGROUND: The prevalence of hepatitis B virus (HBV) infection is high in Asian countries. Little is known about outcome of leukemia in HBV infected patients in these regions. Hence, we conducted this study in two cohorts of patients. PROCEDURE: We retrospectively evaluated mortality, reduction in dose intensity and duration of therapy (intensive phase and maintenance phase) in children with acute lymphoblastic leukemia (ALL) who developed HBV infection. Sixty-three patients with ALL were included in the retrospective cohort of the study. These were followed up for a minimum of 5 years. We prospectively investigated the prevalence of anti-HBc antibodies in 105 treatment naïve pediatric patients with ALL and negative for HbsAg. RESULTS: Twenty of the 63 patients developed hepatitis, of which 10 were attributed to HBV. All the 10 patients with HBV hepatitis had significantly reduced dose intensity during maintenance therapy with an average delay in completion of therapy of 140 ± 83 days and also a high mortality (40%). In the prospective cohort of the study, 39% of treatment naive patients who were HBsAg negative were anti-HBc positive at presentation, possibly reflecting occult HBV infection. CONCLUSIONS: HBV infection poses a serious problem in patients with ALL. Hence we propose that in India, in addition to screening for HBsAg, patients with leukemia should also be screened for anti-HBc. Improved hepatitis B vaccine coverage in the community under the universal immunization programme and introduction of HBV nucleic acid test (NAT) for blood donations should also help in addressing the problem.

Cancer notification in India.

In many developed countries, notification of cancer cases is compulsory. Developing countries including India accounts for more than half of new cancer cases in the world, however notification of cancer is not yet mandatory. The primary purpose of notification is to effect prevention and control and better utilization of resources. It is also a valuable source for incidence, prevalence, mortality and morbidity of the disease. Notification of cancer will lead to improved awareness of common etiologic agents, better understanding of common preventable causes and better utilization of health resources with better monitoring and evaluation of the effectiveness of health programs such as cancer screening and cancer treatment programs, which ultimately might improve survival. Notification of cancer can be done by the doctor or the hospital. Akin to the integrated disease surveillance project where more than 90% of the districts report weekly data through E-mail/portal, notification of cancer can be implemented if it is incorporated into the National Program for Prevention and Control of Cancer, Diabetes, Cardiovascular diseases and Stroke scheme. The need of the hour is cancer notification in India.

The response of Paracoccus sp. SKG to acetonitrile-induced oxidative stress.

Organic solvents enhance intracellular oxidative stress and induce various physiological responses in bacteria. The study shows the morphological changes in Paracoccus sp. SKG when exposed to higher concentrations of acetonitrile, which alter the composition of the membrane fatty acid that accompanies the increase in K(+) efflux. This enhances the oxidative stress with greater activities of catalase and super oxide dismutase (SOD). The increased oxidative stress results in the generation of free radicals, which was confirmed by electron paramagnetic resonance (EPR) studies. The free radical scavenging activities were measured by ABTS and DPPH to understand the non-enzymatic defensive system during oxidative stress. The studies demonstrate the increase in free radicals in association with enzymatic and non-enzymatic defense systems under solvent stress.

Risk strata-based therapy and outcome in stage Ib-IIa carcinoma cervix: single-centre ten-year experience.

AIM: To review the outcome of stage (Ib, IIa), cervical cancer patients were primarily treated with radical hysterectomy and risk-based postoperative therapy. MATERIAL AND METHODS: Between January 2001 and December 2011, 601 cases underwent surgery followed by tailored therapy. Patients were classified into low risk (pelvic lymph node negative, tumour less than 4 cm, no evidence of lympho-vascular invasion, less than one-third of thickness of surgical stoma involved), intermediate risk (positive lympho-vascular space invasion, tumour size more than 4 cm, and deep invasion of cervical stroma), and high risk (pelvic lymph node involved, positive parametrial, or vaginal margins) groups. Postoperative adju-vant therapy in the form of radiotherapy alone to those with intermediate risk and chemo-radiotherapy to those with high risk was given to patients. The median follow-up was 60 months. RESULTS: The majority of patients had intermediate risk. The overall event-free survival (EFS) at five years was 74.37%, with EFS of 86.5% in those from the low-risk group, 73% in those from the intermediate-risk group, and 64% in those from the high-risk group. In conclusion, risk strata-based adjuvant postoperative therapy is able to provide a favourable outcome in patients with stage Ib-IIa cervical cancer with a nearly 11% improvement in survival compared with historical control.

Primary non-Hodgkin's lymphoma of bone: poly-ostotic versus mono-ostotic subtypes.

Primary non-Hodgkin's lymphoma of bone (PNHLB) accounts for less than 5% of all primary bone tumours and less than 1% of all non-Hodgkin's lymphoma. Due to its rarity, only a few retrospective studies have been published describing the prognosis and its treatment. We report our experience of 20 cases of PNHLB with their clinicopathologic correlation that were treated at our centre over a period of ten years. There were 16 cases of the mono-ostotic subtype and four cases of poly-ostotic subtype. All of these had a histological diagnosis of diffuse large B-cell lymphoma. The age of presentation was fifth to sixth decade. The mono-ostotic subtype commonly presented with the involvement of femur or humerus, while the poly-ostotic subtype commonly had paraparesis due to vertebral involvement. Cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-based chemotherapy was given to all patients, but definitive radiotherapy was used only in the mono-ostotic subtype. At median follow-up of 38 months (range 5-96 months), event-free survival was 81% and 25% with mono-ostotic and poly-ostotic subtypes, respectively. Thus poly-ostotic PNHLB is a distinctive entity with a poor prognosis, and larger studies are needed for better management of this subtype.

Malignant mixed Mullerian tumour of the uterus.

BACKGROUND: A malignant mixed Mullerian tumour (MMMT) of the uterine corpus is an extremely rare and aggressive malignancy. There are very few studies regarding the outcome of MMMT patients in India. Hence, we conducted the present study to analyse the outcome of MMMTs at our institute. OBJECTIVE: To study the clinical profile, prognostic features, and treatment outcome of MMMT with multimodal therapy. METHOD: A five-year retrospective study of the MMMT cases diagnosed and treated at our centre was conducted. Twenty patients with pathological proven diagnosis of MMMT treated at our institute from January 2007 to May 2012 were analysed. These patients underwent comprehensive surgical staging followed by adjuvant therapy in the form of chemotherapy alone or chemoradiotherapy. These patients were analysed for event-free survival (EFS), and their outcomes were correlated with histology, therapy, myometrial invasion, and the stage of disease. RESULTS: A majority of these patients presented with postmenopausal bleeding. Endometrial biopsy was diagnostic in only 20% of the patients. Of the 20 patients who underwent surgery, 18 patients received adjuvant therapy. At median follow-up of 16 months (range 3-30 months), the EFS was 30%. No difference in outcome was noted based on tumour histology (heterologous versus homologous). Concurrent chemoradiation improves local control and may delay recurrence but has shown little survival advantage. CONCLUSION: MMMT is an aggressive tumour of the uterine corpus. A negative endometrial biopsy does not rule out the diagnosis. Poor outcome is noted in patients with advanced-stage disease and myometrial invasion. The optimal adjuvant treatment for this uncommon disease is yet to be established, highlighting the need for larger multicentric studies on MMMTs.

Indole-3-acetic acid biosynthesis in Fusarium delphinoides strain GPK, a causal agent of Wilt in Chickpea.

Fusarium delphinoides (Ascomycota; Nectriaceae) is an indole-3-acetic acid (IAA) producing plant pathogen and a causal agent of wilt in chickpea. The IAA biosynthetic pathway in F. delphinoides strain GPK (FDG) was examined by analyzing metabolic intermediates and by feeding experiments. Gas chromatograph (GC) analysis of FDG culture filtrates showed the presence of metabolic intermediates of indole-3-pyruvic acid (IPyA), indole-3-acetamide (IAM), and tryptamine (TRA) pathways. The different IAA biosynthetic pathways were further confirmed by identifying the presence of different enzymes of these pathways. Substrate specificity study of aromatic amino acid aminotransferase revealed that the enzyme is highly specific for tryptophan (Trp) and α-ketoglutarate (α-kg) as amino group donor and acceptor, respectively. Furthermore, the concentration-dependent effect of exogenous IAA on fungal growth was established. Low concentration of exogenous IAA increases the fungal growth and at high concentration it decreases the growth of FDG.

The role of surgery in locally advanced carcinoma of cervix after sub-optimal chemoradiation: Indian scenario.

BACKGROUND: Standard treatment of advanced cervical cancer is concurrent chemoradiation. Radical radiotherapy for carcinoma cervix includes pelvic external beam radiotherapy (EBRT) with the concomitant platinum based chemotherapy followed by intracavitary brachytherapy (ICBT) to boost central disease. Management of patients who are suboptimally treated, especially, after unsuccessful ICBT insertion is not well-defined. This study explores the role of hysterectomy in these patients. MATERIALS AND METHODS: From January 2006 to December 2011, 38 patients with locally advanced cervical cancer, in whom ICBT insertion was unsuccessful, were analyzed retrospectively. Operable patients with no parametrial involvement underwent hysterectomy and outcomes (recurrence free and overall survival) were noted. RESULTS: The major complications in post operative period were wound infection, paralytic ileus and bladder atony all of which were conservatively managed with no mortality. At median follow-up of 36 months (range 12-60 months) there was no recurrence in patients with stage 1B2 and stage IIA, 25 out of 38 (65.8%) were event free and the overall survival was 71%. CONCLUSION: Many patients in Indian scenario receive suboptimal therapy in locally advanced cervical cancer. EBRT with chemotherapy followed by type 1 extra-fascial hysterectomy can be a good alternative for these patients.

Anaplastic large cell lymphoma: a single institution experience from India.

BACKGROUND: Systemic anaplastic large cell lymphoma (ALCL) accounts for 2-8% of non-Hodgkin's lymphoma in adults and 10-15% in children. While there is ample data in the world literature about the clinical features and outcome of this disease, prognosis in Indian patients is largely unknown. OBJECTIVE: To study the clinical, pathologic profile and outcome ALCL. MATERIALS AND METHODS: Fifty patients who had pathologically proven diagnosis of systemic ALCL at our institute from June 2003 to May 2011 were included for retrospective analysis. This included 30 cases of anaplastic lymphoma kinase+ (ALK+), ALCL and 20 cases of anaplastic lymphoma kinase- (ALK-), ALCL. The hospital protocol for treatment of these patients included CHOP chemotherapy regimen in >15 years of age and MCP842 protocol with vinblastine for 1 year in <15 years of age. Event free survival was noted. These outcomes were correlated with ALK status, International Prognostic Index (IPI) score, and stage at presentation. RESULTS: At a median follow-up of 36 months (range: 6-72 months) ALK- ALCL had a poor outcome. The 3 year event free survival in pediatric ALCL was 66.7%. In adults, this was 60% ALK+ ALCL was 60% and 20% in ALK- ALCL. CONCLUSIONS: Systemic ALCL is an aggressive disease. CD3 + positivity is commonly seen in ALK- ALCL and ALK+, epithelial membrane antigen + positivity is seen in ALK+ ALCL. ALK- ALCL, advanced stage III, IV and high IPI score were associated with poor prognosis. The demographic profile and outcome in our study was similar to the world literature. With new drugs like crizotinib and brentuximab vedotin the future looks very promising.

Wilms' tumor: single centre retrospective study from South India.

Wilms' tumor is the most common malignant renal tumor in paediatric age group, and is classically managed by multimodal treatment which involves surgery, radiotherapy and chemotherapy. The last few decades have seen a dramatic change in the prognosis of this disease, which once was a uniformly lethal malignancy. While there is plenty of data in world literature on the outcome of Wilms' tumor, there is paucity of data from India. Hence, we conducted the present study to analyze the outcome of Wilms' tumor at our institute. To study the clinicopathologic profile and outcome of Wilms' tumor with NWTS (National Wilms' Tumor Study Group) IV protocol. Sixty-one patients with histopathological proven diagnosis of Wilms' tumor and had received treatment at our institute from Jan 2003 through Dec 2010 were included for analysis. Patients received treatment based on NWTS IV protocol. Patients were analysed for overall survival and event free survival and these outcomes were correlated with age, sex, stage at presentation and histology. Favourable histology which included focal anaplasia was found in 80.3 % while unfavourable histology was elicited in 19.7 % of the cases. The estimated 5 year event-free survival was 83.3 % and overall survival was 85.2 %. Tumour histology was the single most important factor predicting the survival. Patients with childhood Wilms' still present very late in our setting, this poses management challenges as large tumor are technically difficult to deliver at surgery. Histology has a crucial role in outcome of this disease. With multidisciplinary approach, similar survival rates to National Wilms' Tumor Study Group seems to be achievable even in Indian scenario.

Paediatric nasopharyngeal carcinoma: an 8-year study from a tertiary care cancer centre in South India.

Nasopharyngeal carcinoma (NPC) accounts for less than 1 % of all paediatric cancers. Advances in imaging, radiation delivery, chemotherapy and improvement in multidisciplinary care have resulted in drastic changes in the outcome of this disease. Since NPC is extremely rare in paediatric population and there is paucity of data in Indian patients, we conducted the present study to analyze the outcome of paediatric NPC. Eighteen patients aged 18 years or less, who had pathologically proven diagnosis of NPC and had received treatment at our institute from 2003 to 2010 was included for analysis. These patients were treated with radiotherapy and chemotherapy. Event free survival, local and systemic relapse and progression were analysed. These outcomes were correlated with age, radiation dose and the stage of disease. Majority of patients presented with advanced stage and poor histological grade (94.4 % had WHO Type III disease). The median follow up was 38 months (range 3-91 months). The estimated event free survival at a follow up of 5 years was 64.28 %. Distant metastasis at presentation and lower radiation dose were predictive of poor outcome. Paediatric NPC usually presents in an advanced stage. Our results are comparable to studies which have used only chemoradiotherapy, are far inferior to studies which have used chemoradiotherapy and adjuvant immunotherapy. Larger prospective studies are required to define the role of adjuvant immunotherapy, the optimum dose and schedule of chemoradiotherapy and role of new agents like cetuximab in Indian paediatric patients.

Prevalence of undiagnosed HIV infection in patients with ocular surface squamous neoplasia in a tertiary center in Karnataka, South India.

PURPOSE: To evaluate the prevalence of undiagnosed and asymptomatic human immunodeficiency virus (HIV) infection in patients with ocular surface squamous neoplasia (OSSN) in a referral hospital in Karnataka, South India. METHODS: A consecutive series of patients presenting with OSSN were evaluated in an academic center during January 2009 to June 2010. A detailed history was obtained and physical examination in 25 consecutive patients with OSSN was performed. Twenty-three patients (88%) agreed to undergo serological HIV testing. Of these, 2 were excluded from the current study because they had xeroderma pigmentosa, a known predisposing factor for OSSN. RESULTS: Of the 21 patients, 6 (29%) patients were HIV positive. None of the patients had previous HIV testing. The median age of presentation among HIV-positive patients was 36 years, whereas it was 54 years among HIV-negative patients. The mean CD4 count in HIV-positive patients was 133 cells per mm, and all patients were started on antiretroviral treatment. CONCLUSIONS: The conjunctival tumor may be the primary and the only apparent manifestation of HIV in patients presenting with OSSN, and the ophthalmologist needs to be aware of this association.

Atorvastatin exhibits anti-inflammatory and anti-oxidant properties in adjuvant-induced monoarthritis.

Arthritis is a joint disorder where the joint damage is associated with elevated levels of inflammatory mediators and reactive oxygen species (ROS). The inflammatory hyperalgesia associated with arthritis has been shown to be attenuated by anti-hyperlipidemic drug, atorvastatin. The present study was carried out to evaluate the effect of atorvastatin on joint inflammation and associated oxidative stress markers in a rat model where arthritis was induced by intra-articular injection of 0.1 ml of 0.1% Freund's Complete Adjuvant (FCA). Atorvastatin (10 mg and 50 mg/kg) and diclofenac (5 mg/kg) were administered orally, daily during the study period of 4 days and their effect on joint inflammation was evaluated by measuring joint diameter, levels of glutathione (GSH), thiobarbituric acid reactive substances (TBARS), activity of super oxide dismutase (SOD) and tissue histology. Atorvastatin produced a dose-dependent reduction in joint inflammation that was associated with normalization of levels of oxidative stress markers and tissue histology and its effect was found to be comparable to that of diclofenac.