Voltage-activated currents and their modulation in somatic muscle cells of the nematode Ascaris suum

Voltage-activated currents have been isolated in nematodes and are associated with depolarization (calcium channels) or recovery of the cell after the depolarization (potassium channels). Different subtypes of voltage-activated calcium channel have been identified in vertebrates. In nematodes, advances in C. elegans genomics led to the identification of voltage-activated calcium channel subtypes. These subtypes show homologies to vertebrate calcium channels but are pharmacologically and physiologically different. The understanding of the physiology of these different voltage-activated channels is becoming increasingly important as we try to lower the development of resistance to present anthelmintics. Major classes of anthelmintics produce their effect by modulating neuromuscular system either indirectly or directly. Therefore, it is important for us to understand the physiology of these channels in the worms to either identify novel drug target sites or understand the mechanism of development of resistance. Recently a new class of anthelmintic compounds, cyclo-octadepsipeptides, has been released for animal use. There modes of action include, latrophillin receptors activation, PF1 like neuropeptide release and more recently demonstrated activation of voltage-activated calcium dependent potassium channels. It is known from previous work done in A. suum and C. elegans that there are voltage-activated channels on the muscle membrane. Electrophysiological recordings in A. suum and other nematodes have shown that these currents may be modulated by different anthelmintics. We used voltage-clamp and current-clamp techniques to study voltage-activated currents in the pig parasitic nematode A. suum somatic muscle cells. We were able to isolate two types of voltage-activated calcium currents and one type of outward potassium current. We have characterized these channels pharmacologically and kinetically. We also realized that these channels, if modulated, could potentiate the response of cholinergic anthelmintics. Further, we used different endogenous nematode neuropeptides to modulate these currents.;Neuropeptides and their receptors offer novel drug target sites, not only for the development of new anthelmintics, but also to increase the potency of existing drugs. We anticipate that our observations will increase the understanding of worm physiology and validate the potential for exploring neuropeptide receptors for anthelmintic chemotherapy

Fractal dimension for Inhomogeneous graph-directed attractors

In this paper, we define inhomogeneous Graph-Directed (GD) separation conditions for a given inhomogeneous GD Iterated Function Systems (IFS), and estimate the upper box dimension of attractors by the dimension of the condensation set and associated Mauldin-Williams graph dimension. Following some work of Fraser, we also estimate the lower box dimension of attractors generated by inhomogeneous GDIFS. In the end, we shed few lights on the continuity of dimensions for the attractors of inhomogeneous GDIFS.Comment: 14 pages, 1 figur

DOCKING STUDIES OF SUBSTITUTED CHROMAN ANALOGS AT ESTROGEN RECEPTOR

Objective: The objective of the present study is to perform the molecular docking studies of some newly designed chroman analogs on estrogenreceptor (ER) (PDB: 1YIM) by Glide v5.0.Methods: The docking studies of designed chroman analogs were performed on the active site of ER (PDB: 1YIM) for anti-breast cancer activity usingSchrodinger Glide v5.0. Absorption, distribution, metabolism, excretion properties of all designed compounds were also calculated by Qik Prop v3. 0.Results: Among all compounds, compound 38 showed highest docking score (−8.17) in the series. Docking scores were compared with standarddrugs tamoxifene (−11.08) and anastrazole (−7.86). All compounds were found to be within expectable range for percent human oral absorption,octanol/water partition coefficient (QP log Po/w), brain/blood partition coefficient (QP log BB), total solvent accessible surface area, and rule of fivepredicted by Qikprop.Conclusion: Most of the compounds in the series showed good molecular docking score on the ER (PDB: 1YIM). Compound 38 (−8.16) exhibitedbetter docking score than standard drug anastrazole (−7.86). Most of the pharmacokinetic properties conducted by Qikprop were found to be withinthe permissible range.Keywords: Chroman, Docking, Estrogen receptor, Lipinski's rule of five

A case report on Duchene muscular dystrophy in an Indian family

Duchenne muscular dystrophy (DMD) is commonest X-linked syndrome muscular dystrophy in the children, present in early childhood and characterized by the proximal muscle weakness and the calf hypertrophy in exaggerated boys. There is generally delay in the motor development and ultimately wheelchair confinement leading to premature death from cardiac or the respiratory complications. For treatment we use various modalities like corticosteroid therapy. We also used intermittent positive pressure ventilation that could help in developments in function, quality of life, ambulation and life expectancy though novel therapies still focus to provide the cure for this disease. Clinically, it is categorized by the progressive muscle wasting ultimately leading to the premature death. Here we presented a case of Duchene muscular dystrophy in a 13 year old boy with clinical presentation