Primary empty sella with isolated ACTH deficiency and microprolactinoma

The empty sella turcica is defined as the herniation of the subarachnoid space within the sella with displacement of the pituitary towards the posteroinferior wall. By autopsy studies, the incidence in the general population is around 20%. The association of prolactinoma and empty sella has been coincidental & infrequently reported. As such for microadenoma, visual field testing and screening for hypopituitarism is not needed, but if it is associated with empty sella, both visual field testing and screening for hypopituitarism is necessary.     

Computational validation of 3-ammonio-3-(4-oxido- 1H-imidazol-1-ium-5-yl) propane-1, 1-bis (olate) as a potent anti-tubercular drug against mt-MetAP

The advent of Multi Drug Resistant (MDR) strain of Mycobacterium tuberculosis (TB) necessitated search for new drug targets for the bacterium. It is reported that 3.3% of all new tuberculosis cases had multidrug resistance (MDR-TB) in 2009 and each year, about 0.44 million MDR-TB cases are estimated to emerge and 0.15 million people with MDR-TB die. Keeping such an alarming situation under consideration we wanted to design suitable anti tubercular molecules for new target using computational tools. In the work Methionine aminopeptidase (MetAP) of Mycobacterium tuberculosis was considered as target and three non-toxic phenolic=ketonic compounds were considered as ligands. Docking was done with Flex X and AutoDock 4.2 separately. Ten proven inhibitors of MetAP were collected from literature with their IC50 and were correlated using EasyQSAR to generate QSAR model. Activity of ligands in question was predicted from QSAR. Pharmacophore for each docking was generated using Ligandscout 3.0. Toxicity of the ligands in question was predicted on Mobyle@rpbs portal and Actelion property explorer. Molecular docking with target showed that of all three ligands, 3-ammonio-3-(4-oxido-1H-imidazol-1-ium-5-yl) propane-1, 1-bis (olate) has highest affinity (- 37.5096) and lowest IC50 (4.46 µM). We therefore, propose that -3-ammonio-3-(4-oxido-1H-imidazol-1-ium-5-yl) propane-1,1- bis(olate) as a potent MetAP inhibitor may be a new anti-tubercular drug particularly in the context of Multi Drug Resistant Tuberculosis (MDR-TB).     

Atherogenic effect of Arecoline: A computational study

There are over 600 million people worldwide covering Asian and Oceanic countries including India have the habit of chewing areca nut as masticator in different forms. Arecoline (C(8)H(13)NO(2)) has been reported as one of the abundant constituents of areca nut. A good number of scientific publications have made Arecoline responsible for oral cancer. Based on observation from clinical situation in North East India, one of the most betel quid chewing region of the country, we suspected a link between consumption of areca nut and Cerebro Vascular Disease like stroke. Therefore, we considered Low Density Lipoprotein (LDL) receptor as target and Arecoline as ligand and studied ligand -target interaction using computational tools. Also we considered High Density Lipoprotein (HDL) receptor as another target to see if Arecoline has any binding potential with it over and above LDL receptor. Docking result indicated that Arecoline and Cholesterol both, have affinity towards extracellular domain of Human LDL receptor but affinity of Arecoline is much higher (-12.3560.) than that of Cholesterol(-0.1810). Docking of Arecoline and 1, 2-Hexyl-1- cyclopentanone thiosemicarbazone (thiosemicarbazone) with Bovine HDL receptor showed that Arecoline also has the potential (Score, -6.2690Kcal/Mol) to block HDL receptor though its potential is less than that (score, -10.0509 Kcal/Mol) of control (thiosemicarbazone). We, therefore, suggest that by inhibiting endocytosis of LDL cholesterol because of blocking LDL receptor function and also by preventing LDL cholesterol uptake by liver from blood because of interference with HDL receptor, Arecoline may contribute to atherosclerosis. The study therefore, indicates a positive correlation between chewing of betel quid and Cerebro Vascular Disease.     

NeMedPlant: a database of therapeutic applications and chemical constituents of medicinal plants from north-east region of India

The North-East region of India is one of the twelve mega biodiversity region, containing many rare and endangered species. A curated database of medicinal and aromatic plants from the regions called NeMedPlant is developed. The database contains traditional, scientific and medicinal information about plants and their active constituents, obtained from scholarly literature and local sources. The database is cross-linked with major biochemical databases and analytical tools. The integrated database provides resource for investigations into hitherto unexplored medicinal plants and serves to speed up the discovery of natural productsbased drugs. AVAILABILITY: The database is available for free at http://bif.uohyd.ac.in/nemedplant/orhttp://202.41.85.11/nemedplant/     

Production and characterization of pharmacologically active recombinant human phosphodiesterase 4B in Dictyostelium discoideum

Phosphodiesterase 4B (PDE4B) is an important therapeutic target for asthma and chronic obstructive pulmonary disease. To identify PDE4 subtype-specific compounds using high-throughput assays, full-length recombinant PDE4 proteins are needed in bulk quantity. In the present study, full-length human PDE4B2 was expressed in the cellular slime mould Dictyostelium discoideum (Dd). A cell density of 2 x 10(7) cells/mL was obtained and up to 1 mg/L recombinant PDE4B2 was purified through Ni-NTA affinity chromatography. The expressed protein was soluble and its activity was comparable to PDE4B2 protein expressed in mammalian cells (K(m)=1.7 microM). The functional significance of the Dd expression system is supported by the demonstration that, in concert with proteins expressed in mammalian systems, there are no major changes in the affinity for PDE4B2 inhibitors and substrates. These findings thus provide the first evidence that Dd can be utilized for the expression and purification of functionally active full-length human PDE4B2 in large amounts required for high-throughput screening of pharmacologically active compounds against this therapeutic target.     

In vitro evaluation of antagonistic properties of Pseudomonas corrugata

Pseudomonas corrugata, a soil bacterium originally isolated from a temperate site of Indian Himalayan Region (IHR) is examined for its antagonistic activities against two phytopathogenic fungi, Alternaria alternata and Fusarium oxysporum. Although the bacterium did not show inhibition zones due to production of diffusible antifungal metabolites, a reduction in growth between 58% and 49% in both test fungi, A. alternata and F. oxysporum, was observed in sealed Petri plates after 120 h of incubation due to production of volatile antifungal metabolites. Reduction in biomass of A. alternata (93.8%) and F. oxysporum (76.9%) in Kings B broth was recorded after 48 h of incubation in dual culture. The antagonism was observed to be affected by growth medium, pH and temperature. The reduction in fungal biomass due to antagonism of bacteria was recorded maximum in the middle of the stationary phase after 21 h of inoculation. The production of siderophore, ammonia, lipase and chitinase in growth medium by P. corrugata were considered contributing to the antagonistic activities of the bacterium.     

High-speed imaging of developing heart valves reveals interplay of morphogenesis and function

Knowing how mutations disrupt the interplay between atrioventricular valve (AVV) morphogenesis and function is crucial for understanding how congenital valve defects arise. Here, we use high-speed fluorescence microscopy to investigate AVV morphogenesis in zebrafish at cellular resolution. We find that valve leaflets form directly through a process of invagination, rather than first forming endocardial cushions. There are three phases of valve function in embryonic development. First, the atrioventricular canal (AVC) is closed by the mechanical action of the myocardium, rolls together and then relaxes. The growing valve leaflets serve to block the canal during the roll and, depending on the developmental stage, either expand or hang down as a leaflet to block the canal. These steps are disrupted by the subtle morphological changes that result from inhibiting ErbB-, TGFbeta-or Cox2 (Ptgs2)-dependent signaling. Cox2 inhibition affects valve development due to its effect on myocardial cell size and shape, which changes the morphology of the ventricle and alters valve geometry. Thus, different signaling pathways regulate distinct aspects of the behavior of individual cells during valve morphogenesis, thereby influencing specific facets of valve function.     

Isolation and identification of an endophytic strain of Fusarium oxysporum producing podophyllotoxin from Juniperus recurva

Podophyllotoxin, a well-known naturally occurring aryltetralin lignan occurs in few plant species that is used as a precursor for the chemical synthesis of the anticancer drugs like etoposide, teniposide and etopophose phosphate. The availiability of this lignan is becoming increasingly limited because of the scarce occurance of its natural sources and also because synthetic approaches for its production are still commercially unacceptable. This paper reports first time the production of podophyllotoxin by an endophytic fungus Fusarium oxysporum isolated from the medicinal plant Juniperus recurva. Further confirmation and quantification of podophyllotoxin was performed by HPLC, LC-MS, and LC-MS/MS.