Molecular Docking Studies of Phytocompounds from the Phyllanthus Species as Potential Chronic Pain Modulators

The study of inflammatory pain has been one of the most rapidly advancing and expanding areas of pain research in recent years. Studies from our lab have demonstrated the chronic pain-modulating potential of the Phyllanthus species and their probable interaction with various inflammatory mediators involving enzymes like COX-2 and PGE synthase, cytokines like TNF-alpha and IL-1 beta, and with the NMDA receptor. Inflammatory mediators which play a crucial role in chronic inflammatory hyperalgesia and its subsequent modulation were selected for their interactions with 86 structurally diverse phytoconstituents identified from the Phyllanthus species.The docking analysis of the target proteins with the phytochemical ligands was performed using VLifeMDS software. The docking scores and analysis of the interactions of the phytocompounds with target proteins suggest that important molecules like lupeol, phyllanthin, hypopyllanthin, corilagin, epicatechin, and most of the other compounds have the ability to bind to multiple targets involved in inflammatory hyperalgesia.Our study strongly suggests that the findings of the present study could be exploited in the future for designing ligands in order to obtain novel molecules for the treatment and management of chronic pain.     

Biological activities of the crude skin toxin of the Suez Gulf oriental catfish (Plotosus lineatus) and its antitumor effect in vivo (mice)

Quantitative determination of newly reported enzymes activity in the crude skin toxin (CST) of catfish revealed highest activities of hyaluronidase and lipase, lesser activities of phospholipase A2, lactate dehydrogenase (LDH), cholinesterase (CE), alkaline phosphatase (ALP), and aspartate transaminase (AST), and least activities of proteinase and 5-nucleotidase (5'-NT). The CST has a hemolytic activity of 54% and no ichthyotoxicity up to 500 ug/ml. The chosen dose of CST (LD12.5) showed a potential cytotoxic activity against solid Ehrlich carcinoma-bearing mice demonstrated by an increase in the mean survival time (238.8%) and tumor growth inhibition ratio (T/C) of 73%. The CST ameliorated the relative weights of heart and liver after three weeks, while modulating the elevation in the relative spleen weight throughout the treatment periods (three, six, and nine weeks). The levels of serum triglyceride, total cholesterol, and liver total lipids were normalized after three weeks, whereas the serum albumin and hepatic glycogen concentrations, as well as ALT, AST, 5'-NT, and G-6-Pase activities were ameliorated after 6 weeks. Serum levels of glucose, LDH, and creatine kinase (CK) activities were significantly modulated throughout the treatment periods. Histological examinations of the tumor and liver tissues of treated tumor-bearing animals were carried out. Tumor tissues showed many cytolytic and cytopathic changes after treatment, while liver tissues showed moderate dysplastic changes after six weeks of treatment, which became more marked after nine weeks.     

Volumetric rendering techniques: applications for three-dimensional imaging of the hip

Volumetric rendering is a new approach to three-dimensional (3D) imaging that overcomes many of the drawbacks of currently available surface-rendering systems. Its application on the Pixar Imaging System in two cases of acetabular fracture was assessed to illustrate the features of the technique. The fast-computing architecture and large memory of this system allow rapid generation of a series of high-quality 3D images in each plane of rotation (x or spinal axis, z or somersaulting axis) that can be viewed as independent static images or as an animated real-time video loop. Editing to remove the normal contralateral hemipelvis enhances appreciation of acetabular abnormalities. Every pixel of computed tomographic data is preserved, allowing representation of both soft tissue and bone as translucent overlap. The presentation of data also allows detection of subtle abnormalities and features and minimizes the artifact generation common in surface-rendered images.     

Simulated femoral repositioning with three-dimensional CT

Three-dimensional volumetric rendering of CT data has proven to be valuable in the evaluation of the hip. Although video loop animation allows review of the anatomy from all perspectives, it does not show the functional range of motion of the femur in the acetabulum. We have developed a technique termed simulated dynamic CT that gives dynamic animated three-dimensional viewing capabilities. This technique incorporates static CT data with gait and movement data to produce a sequence of dynamic images simulating range of motion. Additionally, this technique allows simulation of surgical techniques to visually anticipate the results of reduction and traction and potential limitations in subsequent hip movement. To assess the potential of this technique, two dysplastic hip patients were studied prior to reconstruction. In each case the perspective thus gained led to altered surgical management.     

Combined estrogen and ghrelin administration decreases expression of p27<Superscript>kip1</Superscript> and proportion of isomyosin type I in the striated urethral and anal sphincters and levator ani of old ovariectomized rats

We compared estrogen and/or ghrelin effects on pelvic floor muscles in old versus young adult ovariectomized rats. Ovariectomized Fisher 344 rats (18 and 3 months old, n = 24 x 2) received 42 daily intraperitoneal 17-beta estradiol (10 mug kg(-1)), ghrelin (2 mug kg(-1)), both, or vehicle (n = 6 x 4/group). Cytoplasmic p27(kip1) expression and isomyosin I proportion in striated urethral and anal sphincters and levator ani were measured, respectively, by Western blot analysis and gel electrophoresis with immunohistochemistry of muscle ghrelin receptors and radioimmunoassay of circulating growth hormone. In young adult rats, estrogen significantly decreased cytoplasmic p27(kip1) and isomyosin I signal intensities. In old rats, ghrelin and estrogen/ghrelin significantly decreased both intensities with greater estrogen/ghrelin effect. Ghrelin receptors were not immunostained in any muscle. Estrogen and/or ghrelin significantly increased or decreased, respectively, circulating growth hormone in old and young adult rats. Estrogen/ghrelin administration reversed pelvic floor muscle ageing changes in old ovariectomized rats through growth hormone production.     

Pattern of pesticide storage before pesticide self-poisoning in rural Sri Lanka

Background  

Deliberate self-poisoning with agricultural pesticides is the commonest means of suicide in rural Asia. It is mostly impulsive and facilitated by easy access to pesticides. The aim of this large observational study was to investigate the immediate source of pesticides used for self-harm to help inform suicide prevention strategies such as reducing domestic access to pesticides.     

CT of malignant melanoma in the chest, abdomen, and musculoskeletal system

Malignant melanoma is an aggressive neoplasm that can involve virtually every organ system. This article provides a review of the various appearances on computed tomographic (CT) scans of melanoma involving the chest, abdomen, and musculoskeletal system. Specific emphasis is placed on the typical and atypical CT manifestations of disease as well as the similarity of these findings to those for other disease entities. The importance of accurate staging of melanoma is stressed.     

Proximodistal gradients of the postjunctional folds at the frog neuromuscular junction: a scanning electron microscopic study

Frog endplates were studied with the scanning electron microscope following the removal of the presynaptic terminal by collagenase and acid treatments. Endplates had 2-14 branches of primary cleft. The longest branches were parallel to the muscle fiber. Short branches oblique or perpendicular to the muscle fiber were also present near the central region of the endplates. The openings of postjunctional folds in the primary cleft were clearly visible at the bottom of the primary cleft and could be counted and measured. The longest primary cleft branches of each endplate were divided into segments of 20 microns (length corrected for shrinkage). The number of postjunctional folds per micrometer of primary cleft, the average postjunctional fold length (i.e. across the primary cleft) and the total postjunctional fold's length per micrometer of primary cleft were evaluated for each 20-microns segment of primary cleft. Negative proximodistal gradients were observed for these three parameters for the long branches of primary cleft, i.e. values were higher in the proximal region (near the motor axon) than in the distal region. These postsynaptic gradients probably reflect similar or smaller proximodistal presynaptic gradients for the active zones along the nerve.     

Pneumocystis carinii involvement of the liver and spleen: CT demonstration

Patients with acquired immunodeficiency syndrome (AIDS) are subject to a variety of infections, including Mycobacteria avium intracellulare, cytomegalovirus, Cryptosporidium, and Pneumocystis carinii. Pneumocystis is most commonly associated with a potentially fatal pneumonia in AIDS patients. Other organ involvement by Pneumocystis is rare. We present a patient with hepatic and presumed splenic infiltration by Pneumocystis.