Simultaneous presentation of pulmonary tuberculosis and lung cancer: experience from a regional cancer centre

Background: Prevalence of pulmonary tuberculosis is very high in India. Lung cancer is the most common cancer in males in Delhi and because of close similarity in clinical and radiological features of lung cancer and tuberculosis many of lung cancer patients have had received empirical anti tubercular treatment (ATT) before a diagnosis of lung cancer was established. True incidence of pulmonary tuberculosis in lung cancer is not known. Tuberculosis in lung cancer may get reactivated following chemotherapy and/or radiation therapy. Simultaneous presentation of tuberculosis and lung cancer independent of treatment with immunosuppresants, however, is rare. Material and Methods: At our center we evaluated records of 580 lung cancer patients seen over a period of 5 years to see incidence of pulmonary tuberculosis in lung cancer. Patients who had been worked up for pulmonary tuberculosis like sputum or bronchoalveolar lavage (BAL) for AFB smear or culture were identified. Results: Two hundred and ninety eight of these patients were worked up for pulmonary tuberculosis. Twelve patients in the present study had documented evidence of simultaneous existence of pulmonary tuberculosis (acid fast bacilli positive sputum and or culture positivity) and lung cancer. Radiologically, no separate active tubercular lesion was identified except in one patient who had left upper zone fibro parenchymal lesion. Fibrosis and calcification on chest X-rays (CXR) suggestive of old tuberculosis were evident in 7 patients. Eight patients died of progressive lung cancer within 3 months of diagnosis, 4 patients became acid fast bacilli (AFB) negative after 2 months of anti tubercular therapy. Diagnosis of lung cancer was delayed in 4 patients as they were receiving anti tubercular therapy after detection of AFB in sputum. Conclusion: Recognition of tuberculosis is important not only because it is curable but also due to the fact that its presence interferes with radiological assessment to chemotherapy and radiotherapy. Sputum acid fast smear may be done more frequently in patients of lung cancer in countries where tuberculosis has high prevalence. The true incidence may be still higher and newer techniques e.g. PCR based and others may help in knowing true incidence of co existence of lung cancer and pulmonary tuberculosis

Contract Farming, Ecological Change and the Transformations of Reciprocal Gendered Social Relations in Eastern India

Debates on gender and the commodification of land highlight the loss of land rights, intensification of demands on women’s labour, and decline in their decision-making control. Supported by ‘extra-economic forces’ of religious nationalism (Hindutva), such neoliberal interventions are producing new gender ideologies involving a subtle shift from relations of reciprocity to those of subordination. Using data from fine grained fieldwork in Koraput district, Odisha, we analyse the tensions and transformations created jointly by corporate interventions (contract farming of eucalyptus by the paper industry) and religious nationalism in the local landscape. We examine how these phenomena are reshaping relations of asymmetric mutuality between nature and society, and between men and women

2-Deoxy-D-Glucose Treatment Induces Ketogenesis, Sustains Mitochondrial Function, and Reduces Pathology in Female Mouse Model of Alzheimer's Disease

Previously, we demonstrated that mitochondrial bioenergetic deficits preceded Alzheimer's disease (AD) pathology in the female triple-transgenic AD (3xTgAD) mouse model. In parallel, 3xTgAD mice exhibited elevated expression of ketogenic markers, indicating a compensatory mechanism for energy production in brain. This compensatory response to generate an alternative fuel source was temporary and diminished with disease progression. To determine whether this compensatory alternative fuel system could be sustained, we investigated the impact of 2-deoxy-D-glucose (2-DG), a compound known to induce ketogenesis, on bioenergetic function and AD pathology burden in brain. 6-month-old female 3xTgAD mice were fed either a regular diet (AIN-93G) or a diet containing 0.04% 2-DG for 7 weeks. 2-DG diet significantly increased serum ketone body level and brain expression of enzymes required for ketone body metabolism. The 2-DG-induced maintenance of mitochondrial bioenergetics was paralleled by simultaneous reduction in oxidative stress. Further, 2-DG treated mice exhibited a significant reduction of both amyloid precursor protein (APP) and amyloid beta (Aβ) oligomers, which was paralleled by significantly increased α-secretase and decreased γ-secretase expression, indicating that 2-DG induced a shift towards a non-amyloidogenic pathway. In addition, 2-DG increased expression of genes involved in Aβ clearance pathways, degradation, sequestering, and transport. Concomitant with increased bioenergetic capacity and reduced β-amyloid burden, 2-DG significantly increased expression of neurotrophic growth factors, BDNF and NGF. Results of these analyses demonstrate that dietary 2-DG treatment increased ketogenesis and ketone metabolism, enhanced mitochondrial bioenergetic capacity, reduced β-amyloid generation and increased mechanisms of β-amyloid clearance. Further, these data link bioenergetic capacity with β-amyloid generation and demonstrate that β-amyloid burden was dynamic and reversible, as 2-DG reduced activation of the amyloidogenic pathway and increased mechanisms of β-amyloid clearance. Collectively, these data provide preclinical evidence for dietary 2-DG as a disease-modifying intervention to delay progression of bioenergetic deficits in brain and associated β-amyloid burden

Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: mechanism of cell death

Nutrient deprivation has been shown to cause cancer cell death. To exploit nutrient deprivation as anti-cancer therapy, we investigated the effects of the anti-metabolite 2-deoxy-D-glucose on breast cancer cells in vitro. This compound has been shown to inhibit glucose metabolism. Treatment of human breast cancer cell lines with 2-deoxy-D-glucose results in cessation of cell growth in a dose dependent manner. Cell viability as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide conversion assay and clonogenic survival are decreased with 2-deoxy-D-glucose treatment indicating that 2-deoxy-D-glucose causes breast cancer cell death. The cell death induced by 2-deoxy-D-glucose was found to be due to apoptosis as demonstrated by induction of caspase 3 activity and cleavage of poly (ADP-ribose) polymerase. Breast cancer cells treated with 2-deoxy-D-glucose express higher levels of Glut1 transporter protein as measured by Western blot analysis and have increased glucose uptake compared to non-treated breast cancer cells. From these results we conclude that 2-deoxy-D-glucose treatment causes death in human breast cancer cell lines by the activation of the apoptotic pathway. Our data suggest that breast cancer cells treated with 2-deoxy-D-glucose accelerate their own demise by initially expressing high levels of glucose transporter protein, which allows increased uptake of 2-deoxy-D-glucose, and subsequent induction of cell death. These data support the targeting of glucose metabolism as a site for chemotherapeutic intervention by agents such as 2-deoxy-D-glucose

Targeting cancer metabolism: a therapeutic window opens

Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.

Characterising neovascularisation in fracture healing with laser Doppler and micro-CT scanning

Vascularity of the soft tissues around a bone fracture is critical for successful healing, particularly when the vessels in the medullary canal are ruptured. The objective of this work was to use laser Doppler and micro-computer tomography (micro-CT) scanning to characterise neovascularisation of the soft tissues surrounding the fracture during healing. Thirty-two Sprague–Dawley rats underwent mid-shaft osteotomy of the left femur, stabilised with a custom-designed external fixator. Five animals were killed at each of 2, 4 days, 1, 2, 4 and 6 weeks post-operatively. Femoral blood perfusion in the fractured and intact contralateral limbs was measured using laser Doppler scanning pre- and post-operatively and throughout the healing period. At sacrifice, the common iliac artery was cannulated and infused with silicone contrast agent. Micro-CT scans of the femur and adjacent soft tissues revealed vessel characteristics and distribution in relation to the fracture zone. Blood perfusion dropped immediately after surgery and then recovered to greater than the pre-operative level by proliferation of small vessels around the fracture zone. Multi-modal imaging allowed both longitudinal functional and detailed structural analysis of the neovascularisation process

Research Focus in Palliative Care

This brief article on pre-conference CME topic ‘How to plan Research in Palliative Care’ is aimed to provide an overview of the background, concept, domains, present research activities and the future prospect for research opportunities. Advances in Palliative Care are made with a focus to address the quality of medical practice and ‘quality of death’, in those patients who have advanced stage diseases where cure may or may not be possible. The issues which can improve the palliative care delivery and the areas where evidence of practice is still weak can be identified by forming network and collaborative groups for the application of study and research methods in India

The action of a chemical mutagen on a mutable system in maize

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