Evaluation of Cardioprotective Effect of 3,5,3′-Tri-iodo-L-thyronine in Isoproterenol-Induced Cardiotoxicity

T3 (3,5,3′-triiodothyronine) has drawn relatively little attention in relation to cardiovascular (CVS) diseases. The present study was designed to evaluate the cardioprotective action of T3 in isoproterenol-(ISO-) induced cardiac toxicity. Female Wistar rats were exposed with ISO (100 mg/kg, body weight, subcutaneously) for 2 days at the interval of 24 h followed by T3 (3 μg/kg, body weight, orally) treatment for 3 days. Positive control rats received only ISO (100 mg/kg, body weight, subcutaneously) for 2 days at the interval of 24 hrs. Control group animals received normal saline as a vehicle. As expected, ISO-induced significant changes were observed in low-density lipoprotein, total cholesterol, ALT, CK-MB to TCK ratio, and prolongation of QT interval in electrocardiogram, which is toward normalization after T3 treatment. Lower heart weight, upregulation of cardiac myosin heavy chain alpha (MHC-α), and reduced inflammatory cell infiltration, myonecrosis, vacuolar changes, and a trend toward normal cardiac muscle fiber architecture in microscopic examination of cardiac tissue further support the cardioprotective effect of T3

Modulation of morphology and efficacy of new CB1 receptor antagonist using simple and benign polymeric additives

1014-1021The compound 1, [(1H-[1]benzoxepino[5,4-c]pyrazole-3-carboxamide, 8-chloro-1-(2,4-dichlorophenyl)-4,5-dihydro-N- 1-piperidinyl], a known CB1 modulator has been synthesized and characterized by IR, NMR and single Crystal X-ray study. The single crystal study of 1 displays a number of halogen bonds leading to 1-D network along with other weak noncovalent interactions. The CB1 modulator 1 inherently possesses extremely low solubility in water, which makes its application as drug difficult, and this may be attributed to multiple halogen bonds present in the crystal structure. A series of polymer additives, which are Generally Regarded As Safe (GRAS), have been explored to investigate whether they can modulate the halogen bond present in 1 through formation of various non-bonded interactions. Surprisingly, these polymers are found to change crystal morphology, crystal packing while retaining efficacy and bioavailability. The polymer molecular weight is found to play a significant role in crystal morphology modification especially in case of polyethylene glycol (PEG). The formation of new polymorphic forms of 1 and modification of halogen bond has been established using powder X-ray diffraction and IR study, respectively, in case of PEG 4000, PVPK-30, PVA polymers and compound 1 adducts

Modulation of morphology and efficacy of new CB1 receptor antagonist using simple and benign polymeric additives

The compound 1, [(1H-[1]benzoxepino[5,4-c]pyrazole-3-carboxamide, 8-chloro-1-(2,4-dichlorophenyl)-4,5-dihydro-N-1-piperidinyl], a known CB1 modulator has been synthesized and characterized by IR, NMR and single Crystal X-ray study. The single crystal study of 1 displays a number of halogen bonds leading to 1-D network along with other weak non-covalent interactions. The CB1 modulator 1 inherently possesses extremely low solubility in water, which makes its application as drug difficult, and this may be attributed to multiple halogen bonds present in the crystal structure. A series of polymer additives, which are Generally Regarded As Safe (GRAS), have been explored to investigate whether they can modulate the halogen bond present in 1 through formation of various non-bonded interactions. Surprisingly, these polymers are found to change crystal morphology, crystal packing while retaining efficacy and bioavailability. The polymer molecular weight is found to play a significant role in crystal morphology modification especially in case of polyethylene glycol (PEG). The formation of new polymorphic forms of 1 and modification of halogen bond has been established using powder X-ray diffraction and IR study, respectively, in case of PEG 4000, PVPK-30, PVA polymers and compound 1 adducts.

NMR Crystallography at Fast Magic-Angle Spinning Frequencies: Application of Novel Recoupling Methods

Chemical characterisation of active pharmaceutical compounds can be challenging, especially when these molecules exhibit tautomeric or desmotropic behaviour. The complexity can increase manyfold if these molecules are not susceptible to crystallisation. Solid-state NMR has been employed effectively for characterising such molecules. However, characterisation of a molecule is just a first step in identifying the differences in the crystalline structure. 1 H solid-state Nuclear Magnetic Resonance (ssNMR) studies on these molecules at fast magic-angle-spinning frequencies can provide a wealth of information and may be used along with ab initio calculations to predict the crystal structure in the absence of X-ray crystallographic studies. In this work, we attempted to use solid-state NMR to measure 1 H - 1 H distances that can be used as restraints for crystal structure calculations. We performed studies on the desmotropic forms of albendazole

Interplay between faulting and base level in the development of Himalayan frontal fold topography.

Fold topography preserves a potentially accessible record of the structure and evolution of an underlying thrust fault system, provided we understand the factors that shape that topography. Here we examine the morphology and fault geometry of two active folds at the northwest Himalayan front. The Chandigarh and Mohand anticlines show the following patterns: (1) most (similar to 60%-70%) growth in catchment size and relief (across multiple scales) is accomplished within similar to 5 km of the fault tips, (2) range-scale relief is divided unevenly between the fold flanks because of base level contrasts, (3) mean gradients of the uplifting catchments correspond to different flank-averaged rock uplift rates, (4) high hillslope-scale relief coincides with areas of fast rock uplift and stronger lithologies, and (5) existing relief represents only similar to 15% of the total rock eroded since faulting began, implying significant erosion. The first-order fold topography is developed quickly and asymmetrically as a result of fault-generated rock uplift (which sets the space available for the fold and the distribution of rock uplift rates) with some modulation by base level (which affects the erosional response of the landscape to the uplift). A linear rate of growth in catchment relief with range half-width correlates with catchment-averaged rock uplift rate, suggesting that this metric may be used to infer variations in fault dip at depth. In these frontal fold settings, high slip rates, weak uplifting rocks, and rapid erosion may combine to quickly limit the topographic growth of emerging folds and disconnect their morphology from the displacement field