DuCLOX-2/5 inhibition: a promising target for cancer chemoprevention

Cancer is a leading cause of death and major health concern worldwide. The animal and human studies support the presumption that inflammation directs the cancer initiation and progression. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are the key players in the inflammatory cascade contributing towards the angiogenesis, tumor cell invasiveness, and disruption in the pathways of cellular proliferation/apoptosis. Contemporary studies have particularized a promising role of COX-2 and 5-LOX inhibitors in cancer chemoprevention. The present review is a pursuit to define implications of dual COX-2 and 5-LOX (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention.     

Efficacy and safety of tenecteplase in pulmonary embolism

Pulmonary embolism (PE) is a relatively common life-threatening cardiovascular condition associated with significant morbidity and mortality. We present the efficacy and safety data of weight-adjusted tenecteplase in 30 consecutive patients of acute PE. 30 patients (22 male, 8 female) with acute PE were included in the study and divided into three groups: (1) Acute PE complicated by shock stage and/or persistent hypotension (12 patients). (2) RV dilatation and/or dysfunction without hypotension (14 patients). (3) Severe hypoxemia without hypotension and RV dysfunction (4 patients). Predominant symptoms were dyspnoea, cough, chest pain, syncope and haemoptysis, noted in 100 % (30), 40 % (12), 54 % (16), 32 % (9) and 10 % (3) of patients respectively. RV dilatation and dyskinesia were present in 86 %, septal paradoxical movement in 73 % and inferior venacava collapse absent in 53 % of patients respectively. 12 patients presented with acute PE and cardiogenic shock, 14 patients showed RV dilatation and dysfunction with systolic BP >90 mmHg and four patients were having RV dilation without dysfunction but severe hypoxemia. There was significant reduction in right ventricular systolic pressure and improvement in right ventricular dysfunction. Our study shows that tenecteplase is very effective and safe in the treatment of PE with minimal risk of bleeding in high risk group and intermediate risk and even in selective low risk category group of patients. However, in view of small number of patients in study group, a large multicentre randomized study would be required to draw a firm conclusion regarding the thrombolysis in low risk category patient.     

Synthesis and Evaluation of <Superscript>99m</Superscript>Tc-Labelled Monoclonal Antibody 1D09C3 for Molecular Imaging of Major Histocompatibility Complex Class II Protein Expression

Purpose  

It is known that major histocompatibility complex class II protein HLA-DR is highly expressed in B-cell lymphomas and in a variety of autoimmune and inflammatory diseases. Therefore, a radiolabelled fully humanized IgG4 monoclonal antibody (mAb) can provide useful prognostic and diagnostic information. Aims of the present study were to radiolabel an anti-HLA-DR mAb with technetium-99m and to evaluate its binding specificity, tissue distribution and targeting potential.     

Isolated intramedullary tuberculoma of the dorsal cord: a rare clinico-radiological entity

Tuberculous infection manifesting as an isolated intramedullary tuberculoma of the spinal cord is distinctly unusual. We report a case of a 35 year old woman presenting with an insidious onset of myelopathy, where MRI showed characteristic imaging findings suggestive of intramedullary tuberculosis.     

From the Cover: A Middle Eocene lowland humid subtropical “Shangri-La” ecosystem in central Tibet

Tibet’s ancient topography and its role in climatic and biotic evolution remain speculative due to a paucity of quantitative surface-height measurements through time and space, and sparse fossil records. However, newly discovered fossils from a present elevation of ∼4,850 m in central Tibet improve substantially our knowledge of the ancient Tibetan environment. The 70 plant fossil taxa so far recovered include the first occurrences of several modern Asian lineages and represent a Middle Eocene (∼47 Mya) humid subtropical ecosystem. The fossils not only record the diverse composition of the ancient Tibetan biota, but also allow us to constrain the Middle Eocene land surface height in central Tibet to ∼1,500 ± 900 m, and quantify the prevailing thermal and hydrological regime. This “Shangri-La”–like ecosystem experienced monsoon seasonality with a mean annual temperature of ∼19 °C, and frosts were rare. It contained few Gondwanan taxa, yet was compositionally similar to contemporaneous floras in both North America and Europe. Our discovery quantifies a key part of Tibetan Paleogene topography and climate, and highlights the importance of Tibet in regard to the origin of modern Asian plant species and the evolution of global biodiversity.

The Tibetan Plateau, once thought of as entirely the product of the India–Eurasia collision, is known to have had significant complex relief before the arrival of India early in the Paleogene (1–3). This large region, spanning ∼2.5 million km², is an amalgam of tectonic terranes that impacted Asia long before India’s arrival (4, 5), with each accretion contributing orographic heterogeneity that likely impacted climate in complex ways. During the Paleogene, the Tibetan landscape comprised a high (>4 km) Gangdese mountain range along the southern margin of the Lhasa terrane (2), against which the Himalaya would later rise (6), and a Tanghula upland on the more northerly Qiangtang terrane (7). Separating the Lhasa and Qiangtang blocks is the east–west trending Banggong-Nujiang Suture (BNS), which today hosts several sedimentary basins (e.g., Bangor, Nyima, and Lunpola) where >4 km of Cenozoic sediments have accumulated (8). Although these sediments record the climatic and biotic evolution of central Tibet, their remoteness means fossil collections have been hitherto limited. Recently, we discovered a highly diverse fossil assemblage in the Bangor Basin. These fossils characterize a luxuriant seasonally wet and warm Shangri-La forest that once occupied a deep central Tibetan valley along the BNS, and provide a unique opportunity for understanding the evolutionary history of Asian biodiversity, as well as for quantifying the paleoenvironment of central Tibet.^*Details of the topographic evolution of Tibet are still unclear despite decades of investigation (4, 5). Isotopic compositions of carbonates recovered from sediments in some parts of central Tibet have been interpreted in terms of high (>4 km) Paleogene elevations and aridity (9, 10), but those same successions have yielded isolated mammal (11), fish (12), plant (13–18), and biomarker remains (19) more indicative of a low (≤3-km) humid environment, but how low is poorly quantified. Given the complex assembly of Tibet, it is difficult to explain how a plateau might have formed so early and then remained as a surface of low relief during subsequent compression from India (20). Recent evidence from a climate model-mediated interpretation of palm fossils constrains the BNS elevation to below 2.3 km in the Late Paleogene (16), but more precise paleoelevation estimates are required. Further fossil discoveries, especially from earlier in the BNS sedimentary records, would document better the evolution of the Tibetan biota, as well as informing our understanding of the elevation and climate in an area that now occupies the center of the Tibetan Plateau.Our work shows that the BNS hosted a diverse subtropical ecosystem at ∼47 Ma, and this means the area must have been both low and humid. The diversity of the fossil flora allows us to 1) document floristic links to other parts of the Northern Hemisphere, 2) characterize the prevailing paleoclimate, and 3) quantify the elevation at which the vegetation grew. We propose that the “high and dry” central Tibet inferred from some isotope paleoaltimetry (9, 10) reflects a “phantom” elevated paleosurface (20) because fractionation over the bounding mountains allowed only isotopically light moist air to enter the valley, giving a false indication of a high elevation (21).