ATP allosterically activates the human 5-lipoxygenase molecular mechanism of arachidonic acid and 5(S)-hydroperoxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid.

5-Lipoxygenase (5-LOX) reacts with arachidonic acid (AA) to first generate 5(S)-hydroperoxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid [5(S)-HpETE] and then an epoxide from 5(S)-HpETE to form leukotriene A4, from a single polyunsaturated fatty acid. This work investigates the kinetic mechanism of these two processes and the role of ATP in their activation. Specifically, it was determined that epoxidation of 5(S)-HpETE (dehydration of the hydroperoxide) has a rate of substrate capture (Vmax/Km) significantly lower than that of AA hydroperoxidation (oxidation of AA to form the hydroperoxide); however, hyperbolic kinetic parameters for ATP activation indicate a similar activation for AA and 5(S)-HpETE. Solvent isotope effect results for both hydroperoxidation and epoxidation indicate that a specific step in its molecular mechanism is changed, possibly because of a lowering of the dependence of the rate-limiting step on hydrogen atom abstraction and an increase in the dependency on hydrogen bond rearrangement. Therefore, changes in ATP concentration in the cell could affect the production of 5-LOX products, such as leukotrienes and lipoxins, and thus have wide implications for the regulation of cellular inflammation

A Bayesian investigation of the neutron star equation-of-state vs. gravity degeneracy

Despite its elegance, the theory of General Relativity is subject to experimental, observational, and theoretical scrutiny to arrive at tighter constraints or an alternative, more preferred theory. In alternative gravity theories, the macroscopic properties of neutron stars, such as mass, radius, tidal deformability, etc. are modified. This creates a degeneracy between the uncertainties in the equation of state (EoS) and gravity since assuming a different EoS can be mimicked by changing to a different theory of gravity. We formulate a hierarchical Bayesian framework to simultaneously infer the EoS and gravity parameters by combining multiple astrophysical observations. We test this framework for a particular 4D Horndeski scalar-tensor theory originating from higher-dimensional Einstein-Gauss-Bonnet gravity and a set of 20 realistic EoS and place improved constraints on the coupling constant of the theory with current observations. Assuming a large number of observations with upgraded or third-generation detectors, we find that the $A+$ upgrade could place interesting bounds on the coupling constant of the theory, whereas with the LIGO Voyager upgrade or the third-generation detectors (Einstein Telescope and Cosmic Explorer), the degeneracy between EoS and gravity could be resolved with high confidence, even for small deviations from GR.Comment: Comments are welcome

Anesthetic Considerations in Hepatectomies under Hepatic Vascular Control

Background. Hazards of liver surgery have been attenuated by the evolution in methods of hepatic vascular control and the anesthetic management. In this paper, the anesthetic considerations during hepatic vascular occlusion techniques were reviewed. Methods. A Medline literature search using the terms “anesthetic,” “anesthesia,” “liver,” “hepatectomy,” “inflow,” “outflow occlusion,” “Pringle,” “hemodynamic,” “air embolism,” “blood loss,” “transfusion,” “ischemia-reperfusion,” “preconditioning,” was performed. Results. Task-orientated anesthetic management, according to the performed method of hepatic vascular occlusion, ameliorates the surgical outcome and improves the morbidity and mortality rates, following liver surgery. Conclusions. Hepatic vascular occlusion techniques share common anesthetic considerations in terms of preoperative assessment, monitoring, induction, and maintenance of anesthesia. On the other hand, the hemodynamic management, the prevention of vascular air embolism, blood transfusion, and liver injury are plausible when the anesthetic plan is scheduled according to the method of hepatic vascular occlusion performed

Intranodal palisaded myofibroblastoma: a case report

Intranodal palisaded myofibroblastoma is a rare benign soft tissue tumor, almost always arising from inguinal lymph nodes. It usually presents as a painless, slow-growing inguinal mass. We report herein a case of an intranodal palisaded myofibroblastoma occurring in a 36-year-old man. The salient clinicopathologic features of this unusual tumor are presented and the literature is briefly reviewed

Beyond Preconditioning: Postconditioning as an Alternative Technique in the Prevention of Liver Ischemia-Reperfusion Injury

Liver ischemia/reperfusion injury may significantly compromise hepatic postoperative function. Various hepatoprotective methods have been improvised, aiming at attenuating IR injury. With ischemic preconditioning (IPC), the liver is conditioned with a brief ischemic period followed by reperfusion, prior to sustained ischemia. Ischemic postconditioning (IPostC), consisting of intermittent sequential interruptions of blood flow in the early phase of reperfusion, seems to be a more feasible alternative than IPC, since the onset of reperfusion is more predictable. Regarding the potential mechanisms involved, it has been postulated that the slow intermittent oxygenation through controlled reperfusion decreases the burst production of oxygen free radicals, increases antioxidant activity, suppresses neutrophil accumulation, and modulates the apoptotic cascade. Additionally, favorable effects on mitochondrial ultrastructure and function, and upregulation of the cytoprotective properties of nitric oxide, leading to preservation of sinusoidal structure and maintenance of blood flow through the hepatic circulation could also underlie the protection afforded by postconditioning. Clinical studies are required to show whether biochemical and histological improvements afforded by the reperfusion/reocclusion cycles of postconditioning during early reperfusion can be translated to a substantial clinical benefit in liver resection and transplantation settings or to highlight more aspects of its molecular mechanisms

A rare coexistence of adrenal cavernous hemangioma with extramedullar hemopoietic tissue: a case report and brief review of the literature

<p>Abstract</p> <p>Background</p> <p>Cavernous hemangiomas of the adrenal gland are rare, benign, non-functioning neoplastic tumors. To our knowledge, 55 cases have been reported in the literature to date.</p> <p>Case presentation</p> <p>We report the first case of a large, non-functioning adrenal cavernous hemangioma that was incidentally found during the preoperative staging workup of a 75 year old woman with left breast adenocarcinoma. Imaging with US, CT scan and MRI showed a heterogeneous 8 cm mass with non-specific radiological features that was located on the left adrenal gland. The mass was surgically excised and pathology revealed an adrenal hemangioma with areas of extramedullar hemopoiesis.</p> <p>Conclusion</p> <p>Although adrenal hemangiomas are rare and their preoperative diagnosis is difficult, they should always be included in the differential diagnosis of adrenal neoplasms.</p