Lipoprotein associated phospholipase A2 enzyme; possible new roles and inhibition for therapeutic intervention

Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) is a 45-kDa protein of 441 amino acids encoded by the pla2g7 gene in the humans. In the blood it is associated mainly with Low Density Lipoprotein (LDL) and less than 20% is associated with High Density Lipoprotein (HDL). This enzyme is characterized by its ability to specifically hydrolyze PAF as well as glycerophospholipids containing short, truncated, and/or oxidized fatty acyl groups at the sn-2 position of the glycerol backbone. Genetic studies conducted in humans harboring an inactivating mutation at this locus suggest that loss of Lp-PLA2 function is a risk factor for inflammatory and vascular conditions. Consistently, overexpression of Lp-PLA2 has anti-inflammatory or pro-inflammatory actions and anti-atherogenic properties in animal models. This article discusses two simple techniques to estimate Lp-PLA2 activity. New therapeutic agents inhibiting the activity of Lp-PLA2 are being investigated for curative purpose

Cardiovascular and biochemical studies on the effects of thrombin and dabigatran and the interaction with vasopressor molecules

Background: The effect of serine protease thrombin and its directly acting inhibitor dabigatran were evaluated on the heart rate, blood pressure, and phospholipase C (PLC) enzyme activity and the intracellular calcium levels in the platelets.Methods: Heart rate and blood pressure were estimated using electrophysiology equipment.Results: While thrombin was unable to significantly affect the heart rate and blood pressure, the inhibitor dabigatran was able to reduce the heart rate appreciably but its effects on the blood pressure were minimal. The thrombin induced increase in PLC enzyme activity, and intracellular calcium levels were attenuated by dabigatran in the platelets. The posterior pituitary hormone, vasopressin, and the adrenergic agonist noradrenaline were used to stimulate the PLC and calcium levels in platelets.Conclusion: The thrombin inhibitor, dabigatran reduces vascular oxidative stress and inflammation, improves endothelial function, and decreases atherosclerosis in rodents

Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol

<p>Abstract</p> <p>Background</p> <p>Hyperhomocysteinemia (HHcy) and hyperglycemia cause diabetic cardiomyopathy by inducing oxidative stress and attenuating peroxisome proliferator- activated receptor (PPAR) gamma. However, their synergistic contribution is not clear.</p> <p>Methods</p> <p>Diabetic Akita (Ins2+/-) and hyperhomocysteinemic cystathionine beta synthase mutant (CBS+/-) were used for M-mode echocardiography at the age of four and twenty four weeks. The cardiac rings from WT, Akita and hybrid (Ins2+/-/CBS+/-) of Akita and CBS+/- were treated with different doses of acetylcholine (an endothelial dependent vasodilator). High performance liquid chromatography (HPLC) was performed for determining plasma homocysteine (Hcy) level in the above groups. Akita was treated with ciglitazone (CZ) - a PPAR gamma agonist and tempol-an anti-oxidant, separately and their effects on cardiac remodeling were assessed.</p> <p>Results</p> <p>At twenty four week, Akita mice were hyperglycemic and HHcy. They have increased end diastolic diameter (EDD). In their heart PPAR gamma, tissue inhibitor of metalloproteinase-4 (TIMP-4) and anti-oxidant thioredoxin were attenuated whereas matrix metalloproteinase (MMP)-9, TIMP-3 and NADPH oxidase 4 (NOX4) were induced. Interestingly, they showed synergism between HHcy and hyperglycemia for endothelial-myocyte (E-M) uncoupling. Additionally, treatment with CZ alleviated MMP-9 activity and fibrosis, and improved EDD. On the other hand, treatment with tempol reversed cardiac remodeling in part by restoring the expressions of TIMP-3,-4, thioredoxin and MMP-9.</p> <p>Conclusions</p> <p>Endogenous homocysteine exacerbates diabetic cardiomyopathy by attenuating PPAR gamma and inducing E-M uncoupling leading to diastolic dysfunction. PPAR gamma agonist and tempol mitigates oxidative stress and ameliorates diastolic dysfunction in diabetes.</p

Anti-ulcer activity of arachidonic acid (PUFA) oils in different induced ulcer animal models

Background: Ulcers of the lower part of the oesophagus, the stomach and the first part of the duodenum are also known as peptic ulcers. Peptic ulcers can affect people of any age, but they are more common as you get older. There is a focus on research for better tolerated and efficacious anti-ulcer agents.Methods: Effect of anti-ulcer activity of fish oil and Arasco oil was evaluated in different animal models of ulcers i.e. ethanol induced, water immersion and pyloric ligation techniques. The Superoxide dismutase activity in gastric tissue was also ascertained in two groups of animals. The animals received either fish oil (40 µl, PO), Arasco oil (40 µl, PO), omeprazole (20 mg/kg PO) or ranitidine (30 mg/kg PO). The gastro-protection was calculated based on ulcer index, pH and gastric juice volume.Results: The results of this study suggest that poly unsaturated fatty acid (PUFA) contained in fish oil and Arasco oil have moderate anti-ulcer activity although probably lesser in potency than the available anti-ulcer drugs like omeprazole and ranitidine.Conclusion: These  results  have  shown  that  PUFA containing oils  provided  moderate  gastrointestinal  protection  in  all  the induced ulcer models employed. Thus it can be concluded that PUFA containing oils like the Fish oil and Arasco oil have anti-ulcer properties and the mechanisms involved in these actions need to be investigated.

Acetyl salicylic acid augments functional recovery following sciatic nerve crush in mice

Cyclin-dependent kinase 5 (CDK-5) appears to play a significant role in peripheral nerve regeneration as CDK-5 inhibition retards nerve regeneration following nerve crush. Anti-inflammatory drug acetyl salicylic acid elevates CDK-5 and reduces ischemia – reperfusion injury in cultured neurons. In this study we have evaluated the effect of acetyl salicylic acid on functional recovery following sciatic nerve crush in mice. Eighteen Swiss albino mice underwent unilateral sciatic nerve crush. Test animals received acetyl salicylic acid (100 mg/kg/day, n = 6 or 50 mg/kg/day, n = 6) and control animals (n = 6) received normal saline for 14 days following surgery. Functional recovery was assessed with improvement in Sciatic Function Index, nociception and gait. In comparison with normal saline treatment, acetyl salicylic acid (100 mg/kg/day) significantly improved functional recovery following sciatic nerve crush. Anti-inflammatory drug acetyl salicylic acid appears to be a promising agent for treating peripheral nerve injuries and hence elucidation of its neuroprotective pathways is necessary

Ionization Constants of Some Hydroxycoumarins in Dioxane-Water & Ethanol- Water Media

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Practical long-distance quantum key distribution system using decoy levels

Quantum key distribution (QKD) has the potential for widespread real-world applications. To date no secure long-distance experiment has demonstrated the truly practical operation needed to move QKD from the laboratory to the real world due largely to limitations in synchronization and poor detector performance. Here we report results obtained using a fully automated, robust QKD system based on the Bennett Brassard 1984 protocol (BB84) with low-noise superconducting nanowire single-photon detectors (SNSPDs) and decoy levels. Secret key is produced with unconditional security over a record 144.3 km of optical fibre, an increase of more than a factor of five compared to the previous record for unconditionally secure key generation in a practical QKD system.Comment: 9 page

Zircon to monazite phase transition in CeVO4

X-ray diffraction and Raman-scattering measurements on cerium vanadate have been performed up to 12 and 16 GPa, respectively. Experiments reveal that at 5.3 GPa the onset of a pressure-induced irreversible phase transition from the zircon to the monazite structure. Beyond this pressure, diffraction peaks and Raman-active modes of the monazite phase are measured. The zircon to monazite transition in CeVO4 is distinctive among the other rare-earth orthovanadates. We also observed softening of external translational Eg and internal B2g bending modes. We attributed it to mechanical instabilities of zircon phase against the pressure-induced distortion. We additionally report lattice-dynamical and total-energy calculations which are in agreement with the experimental results. Finally, the effect of non-hydrostatic stresses on the structural sequence is studied and the equations of state of different phases are reported.Comment: 45 pages, 8 figures, 8 table

Operative Management of Symptomatic, Metachronous Carotid Body Tumors Involving the Skull Base and Its Neurological Sequelae

A 44-year-old morbidly obese woman with a history of right carotid body tumor (CBT) resection presented with a symptomatic, nonfunctional, left Shamblin-III CBT. Abutment of the skull base precluded distal internal carotid artery control for arterial reconstruction, favoring parent vessel sacrifice after an asymptomatic provocative test. She underwent CBT resection with anticipated sacrifice of cranial nerves X and XII and the common carotid artery and its branches, developing baroreceptor failure syndrome and sequelae of cranial nerve sacrifice. When facing a symptomatic, metachronous CBT abutting the skull base, upfront operative intervention with adjuvant radiation for residual tumor optimizes curative resection

Multi-phonon Raman scattering in GaN nanowires

UV Raman scattering studies show longitudinal optical (LO) mode up to 4th order in wurtzite GaN nanowire system. Frohlich interaction of electron with the long range electrostatic field of ionic bonded GaN gives rise to enhancement in LO phonon modes. Good crystalline quality, as indicated by the crystallographic as well as luminescence studies, is thought to be responsible for this significant observation. Calculated size dependence, incorporating size corrected dielectric constants, of electron-phonon interaction energy agrees well with measured values and also predict stronger interaction energy than that of the bulk for diameter below ~3 nm.Comment: 13 pages, 5 figures, Journa