A review on potential adverse effects associated with Janus-kinase inhibitors

Rheumatoid arthritis (RA) is a chronic, symmetrical, inflammatory autoimmune disease that affects small joints. RA has a population prevalence of 0.5% to 1% in the U.S. The annual cost of care for chronic treatment of RA in the United States is estimated at $12,509. Pharmaceutical companies have developed drugs to treat RA using Janus kinase (JAK) inhibitors. These drugs can have potential adverse effects. Forecasting a better output to JAK inhibitors (JAKI’s). Therapy duration of JAKI’s and Problems regarding to strategies of dose reduction or if the discontinuation of therapy takes place in case of low disease activity. The accurate pharmacological profile and interactions of other drugs with JAKI’s have to establish. Proper safety, efficacy profile of JAKI’s and when administered in combination with DMARD’s. The safety, efficacy data of JAKI’s when compared to non-anti-TNF biologics. Obtaining of experience on JAKI’s that were already existed in the market and further experimental findings on newer compounds and which may clarify many of the aspects which are to be solved in nearer future as these JAKI will have greater application in treatment of RA. Regardless of significant developments in latest years in the pharmacotherapy of RA in the use of JAK inhibitors, yet the adverse effects of JAK inhibitors are unanswered. Therefore, one of the main concerns associated with JAK inhibitor is the potential adverse effects. The challenges can be addressed by clinical pharmacist mediated interventions related to dosing of JAK inhibitors and proper management of adverse drug reactions (ADRs)

Plasmepsin inhibitors: design, synthesis, inhibitory studies and crystal structure analysis

Plasmepsin group of enzymes are key enzymes in the life cycle of malarial parasites. As inhibition of plasmepsins leads to the parasite's death, these enzymes can be utilized as potential drug targets. Although many drugs are available, it has been observed that Plasmodium falciparum, the species that causes most of the malarial infections and subsequent death, has developed resistance against most of the drugs. Based on the cleavage sites of hemglobin, the substrate for plasmepsins, we have designed two compounds (p-nitrobenzoyl-leucine-β -alanine and p-nitrobenzoyl-leucine-isonipecotic acid), synthesized them, solved their crystal structures and studied their inhibitory effect using experimental and theoretical (docking) methods. In this paper, we discuss the synthesis, crystal structures and inhibitory nature of these two compounds which have a potential to inhibit plasmepsins

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings

Effect of exercise therapy on lipid profile and oxidative stress indicators in patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Yoga has been shown to be a simple and economical therapeutic modality that may be considered as a beneficial adjuvant for type 2 diabetes mellitus. This study investigated the impact of Hatha yoga and conventional physical training (PT) exercise regimens on biochemical, oxidative stress indicators and oxidant status in patients with type 2 diabetes.</p> <p>Methods</p> <p>This prospective randomized study consisted of 77 type 2 diabetic patients in the Hatha yoga exercise group that were matched with a similar number of type 2 diabetic patients in the conventional PT exercise and control groups. Biochemical parameters such as fasting blood glucose (FBG), serum total cholesterol (TC), triglycerides, low-density lipoprotein (LDL), very low-density lipoproteins (VLDL) and high-density lipoprotein (HDL) were determined at baseline and at two consecutive three monthly intervals. The oxidative stress indicators (malondialdehyde – MDA, protein oxidation – POX, phospholipase A2 – PLA2 activity) and oxidative status [superoxide dismutase (SOD) and catalase activities] were measured.</p> <p>Results</p> <p>The concentrations of FBG in the Hatha yoga and conventional PT exercise groups after six months decreased by 29.48% and 27.43% respectively (P < 0.0001) and there was a significant reduction in serum TC in both groups (P < 0.0001). The concentrations of VLDL in the managed groups after six months differed significantly from baseline values (P = 0.036). Lipid peroxidation as indicated by MDA significantly decreased by 19.9% and 18.1% in the Hatha yoga and conventional PT exercise groups respectively (P < 0.0001); whilst the activity of SOD significantly increased by 24.08% and 20.18% respectively (P = 0.031). There was no significant difference in the baseline and 6 months activities of PLA2 and catalase after six months although the latter increased by 13.68% and 13.19% in the Hatha yoga and conventional PT exercise groups respectively (P = 0.144).</p> <p>Conclusion</p> <p>The study demonstrate the efficacy of Hatha yoga exercise on fasting blood glucose, lipid profile, oxidative stress markers and antioxidant status in patients with type 2 diabetes and suggest that Hatha yoga exercise and conventional PT exercise may have therapeutic preventative and protective effects on diabetes mellitus by decreasing oxidative stress and improving antioxidant status.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12608000217303</p

EPR, optical, photoluminescence studies of Cr(3+) ions in Li(2)O-Cs(2)O-B(2)O(3) glasses - An evidence of mixed alkali effect

This paper reports the results on mixed alkali effect (MAE) in xLi(2)O-(30-x)Cs(2)O-69.25B(2)O(3) (5 (4)A(2g) of Cr(3+) ions. (C) 2010 Elsevier B.V. All rights reserved

Expression, purification, crystallization and preliminary crystallographic analysis of the diarrhoea-causing and virulence-determining region of rotaviral nonstructural protein NSP4

The region spanning the tetrameric coiled-coil domain and the interspecies-variable virulence-determining region of the cytoplasmic tail of rotaviral nonstructural protein NSP4 has been crystallized. The crystals belong to space group I222, with unit-cell parameters a = 30.70, b = 38.07, c = 181.62 $\AA$ , and contain two molecules in the asymmetric unit. Diffraction data have been collected utilizing a MAR imaging plate to a resolution of 2.2 $\AA$ . The tetramer is generated by the crystallographic dyad along the c axis

EPR and photoluminescence studies on lithium-potassium borophosphate glasses doped with Mn(2+) ions

The mixed alkali borophosphate xLi(2)O-(30-x)K(2)O-35B(2)O(3)-34.5P(2)O(5) (5 (6)A(1g) ground state of Mn(2+) ions

EPR, optical absorption and photoluminescence properties of Cr(3+) ions in lithium borophosphate glasses

Electron paramagnetic resonance (EPR), optical absorption and photoluminescence studies of Cr(3+) ions in lithium borophosphate glasses have been studied. The EPR spectra exhibit two resonance signals with effective g values at g = 4.56 and g = 1.96. These resonance signals are attributed to isolated Cr(3+) ions and exchange coupled Cr(3+) pairs, respectively. The EPR spectra have also been studied at various low temperatures. The population of spin levels (N) participating at resonance signal g = 1.96 has been calculated as a function of temperature. The spin-population (N) is found to be increasing with decrease in temperature. The magnetic susceptibility (chi) was calculated from the EPR data. It is observed that as temperature decreases, chi increases in accordance with Curie-Weiss law. The exchange coupling constant J between Cr(3+) ions is calculated from the relative intensities of g = 1.96 resonance line at various temperatures. The optical absorption spectrum exhibits four bands characteristic of Cr(3+) ions in octahedral symmetry. From the optical absorption spectral data, the crystal field (Dq) and Racah parameters (B and C) have been evaluated. The luminescence spectrum exhibits a red emission peak, which is assigned to a transition from the upper (4)T(2g) (F) -> (4)A(2g) (F) ground state of Cr(3+) ions. The optical band gap is evaluated from the ultraviolet absorption edges. (C) 2010 Elsevier B.V. All rights reserved

EPR and optical absorption studies of Fe(3+) ions in sodium borophosphate glasses

Electron paramagnetic resonance (EPR) and optical absorption spectral investigations have been carried out on Fe(3+) ions doped sodium borophosphate glasses (NaH(2)PO(4)-B(2)O(3)-Fe(2)O(3)) The EPR spectra exhibit resonance signals with effective g values at g = 2 02 g = 4 2 and g = 6 4 The resonance signal at g = 4 2 is due to isolated Fe(3+) ions in site with rhombic symmetry whereas the g = 2 02 resonance is due to Fe(3+). ions coupled by exchange interaction in a distorted octahedral environment The EPR spectra at different temperatures (123-295 K) have also been studied The intensity of the resonance signals decreases with increase in temperature whereas linewidth is found to be Independent of temperature The paramagnetic susceptibility (x) was calculated from the EPR data at various temperatures and the Curie constant (C) and paramagnetic Curie temperature (0(p)) have been evaluated from the 1/f versus T graph The optical absorption spectrum exhibits bands characteristic of Fe(3+) ions in octahedral symmetry The crystal field parameter (Dq) and the Racah interelectronic repulsion parameters (B and C) have also been evaluated and discussed (C) 2010 Elsevier Ltd All rights reserve

Microstructure, mechanical, EPR and optical properties of lithium disilicate glasses and glass-ceramics doped with Mn2+ ions

The microstructure, mechanical, EPR and optical properties of transparent MnO2 doped lithium disilicate (LDS) glass-ceramics prepared by melt quenching and controlled crystallization, have been studied. The microstructure of the glass-ceramics has been characterized using FE-SEM, TEM, FT-IR and XRD techniques. FE-SEM micrographs show elongated, highly interlocked, dense (similar to 80 vol.%) nanocrystals of LDS with an average size similar to 100 nm. XRD and FT-IR studies reveal that the only crystalline phase formed after heat-treatment at 700 degrees C for 1 h is LDS. A good combination of average microhardness similar to 5.6 GPa, high fracture toughness similar to 2.8 MPa m(1/2), 3-point flexural strength similar to 250 MPa and moderate elastic modulus 65 GPa has been obtained. The EPR spectra of both LDS glasses and glass-ceramics exhibit resonance signals with effective g values at g = 4.73, g = 4.10, g = 3.3, and g = 1.98. The resonance signal at g = 1.98 is found to be more intense than the other signals and exhibits hyperfine structure at lower concentration of manganese. From the observed spectrum, the spin-Hamiltonian parameters have been evaluated. In glass samples the optical absorption spectrum exhibits a broad band around similar to 20,320 cm(-1) which has been assigned to the transition (6)A(1g)(S) -> (4)A(1g)(G) (4)Eg(G)-of Mn2+ ions. The cerammed samples upon 394 nm excitation emit a green luminescence (565 nm, (4)T(1)g -> (6)A(1g)(G) transition of Mn2+ ions), and a weak red emission (710 nm). From the ultraviolet absorption edges, the optical bandgap energies (E-opt) were evaluated and are discussed. (C) 2011 Elsevier B. V. All rights reserved