[Hypertension and aeromedical considerations]

Hypertension is the most prevalent risk factor for arterial disease in the industrialized world and is a frequently encountered clinical problem in the aircrew population. Arterial systolic and diastolic blood pressures are continuously varying quantities, influenced by a host of extraneous factors. Aviators with hypertension responsive to life-style modifications should have serial BP rechecks quarterly to semi-annually during the first year to assure success of the lifestyle modifications. Failure to achieve blood pressure control with lifestyle modifications, or an initial blood pressure average exceeding 160 mmHg systolic or 100 mmHg diastolic, requires initiation of pharmacotherapy. In this study we evaluate books, magazines, articles, guidelines and reliable websites related to aeromedical concerns and waiver considerations in aircrew with hypertension. Two major "types" of essential hypertension are generally recognized. One is characterized by suppressed renin activity and sensitivity to dietary sodium, the other by high renin activity and a lack of response to sodium intake. Thiazide diuretics are certainly the initial therapy of choice, particularly for older subjects. Aircrew with blood pressure that is controlled adequately with thiazides, with no other uncontrolled cardiovascular risk factors, and with no evidence of end-organ damage, are usually fit to return to unrestricted flying in military and civilian spheres. ACE inhibitors are an alternative initial choice in younger aviators, are positively indicated in patients with type 2 diabetes, and have no adverse effects on serum lipids. Hydrochlorothiazide [hctz], with or without triamterene or potassium replacement, can be used as a first line agent for treatment of hypertension in designated personnel. ACE inhibitors might have an adverse effect on G-tolerance have not been borne out by experience in either the US Air Force or the Royal Air Force [RAF], and the US Navy accepts these agents for unrestricted flying without G-tolerance testing

[Ankylosing spondylitis in a military aviator]

Ankylosing spondylitis or Marie Strumpell disease, the most common form of the spondyloarthritides, is a chronic inflammatory disease principally involves the hips and axial skeleton and peripheral joints. In addition, in severe forms of disease, systemic involvements such as uveitis, pulmonary fibrosis and aortic insufficiency can be seen. Its onset is insidious, can have extra-articular manifestations, and is diagnosed by clinical suspicion supported by imaging techniques and associated human leukocyte antigen HLA-B27. The disease may present with nonspecific symptoms such as low fever, fatigue and weight loss. The illness commonly affects young adults with a peak of the third decade of life. The male to female ratio is approximately 2 to 3:1. In the aviators, medical problems may induce a large impact on the ability of aircrew,s safety and their duties. Musculoskeletal diseases that affect the joints and range of motion are important when conside aviators as waiver for aircrew members. Non-specific symptoms such as fatigue may decrease tolerance to acceleration forces in military aviators. So flight surgeons must consider severity of disease and adverse reaction of drugs on the flight safety and its impact on health's aviator. In this paper we report a jet pilot with ankylosing spondylitis disease with a good response to treatment with etanercept

Ab-initio and conformational analysis of a potent vegfr-2 inhibitor: a case study on motesanib

Vascular endothelial growth factor receptor-2 [VEGFR-2]; a cell surface receptor for vascular endothelial growth factors, is a key pharmacological target involved in the cell proliferation/angiogenesis. It has been revealed that VEGFR-2 induces proliferation through activation of the extracellular signal-regulated kinases pathway. In this regard, targeting the VEGFR-2 has been considered as an efficient route to develop anti-tumor agents. Motesanib is a small-molecule antagonist of VEGFR-1, 2, and 3 [IC50s; 2 nM, 3 nM, 6 nM, respectively]. It is an experimental drug candidate undergoing clinical trials against some types of cancer. In the present study, Motesanib [AMG 706] was evaluated in terms of its binding energies with individual amino acids of VEGFR-2 active site [amino acid decomposition analysis]. For this purpose, functional B3LYP associated with split valence basis set using polarization functions [Def2-SVP] was used. Comparative Conformational analysis of the ligand in optimized and crystallographic states revealed that Motesanib does not necessarily bind to the VEGFR-2 active site in its minimum energy conformer

Fragment-based binding efficiency indices in bioactive molecular design: a computational approach to BACE-1 inhibitors

One of the most important targets in Alzheimer disease is Beta site amyloid precursor protein cleaving enzyme-1 [BACE-1]. It is a membrane associated protein and is one of the main enzymes responsible for amyloid beta [A beta] production. Up to now, a considerable number of peptidic and non-peptidic inhibitors of BACE-1 have been developed. Recently, small molecule BACE-1 inhibitors have attracted the attention of scientists, because peptidic inhibitors have many pharmacokinetic problems. In the present study, several small molecule BACE-1 inhibitors were extracted from Brookhaven Protein Databank [PDB] and subjected to dissection analysis to achieve constructing fragments. Atom type, hybridization, and bond order were considered for generated constitutional fragments [simplified structures]. AutoDock version 4.2 was applied to dock various chemical fragments into BACE-1 active site. The benefits of such studies have been well revealed in previous reports. On the basis of obtained binding affinities, fragment-based ligand efficiency [LE] indices were estimated. These theoretical binding efficiencies were applied to further elucidate the key structural features of BACE-1 inhibitors. Typical results of the study were elucidated and we suggested the ways these findings might be beneficial to guide rational bioactive molecular developments. Our study confirmed that the evaluation of ligand-receptor interactions in terms of ligand efficiency indices [binding energy per atom and pK[i] per MW] could be a helpful strategy in structure-based drug discovery [SBDD] strategies

Postoperative cardiac arrest due to cardiac surgery complications

To examine the role of anesthetists in the management of cardiac arrest occurring in association with cardiac anesthesia. In this retrospective study we studied the potential performances for each of the relevant incidents among 712 patients undergoing cardiac operations at Golestan and Naft Hospitals Ahwaz between November 2006 and July 2008. Out of total 712 patients undergoing cardiac surgery, cardiac arrest occurred in 28 cases [3.9%] due to different postoperative complications. This included massive bleeding [50% of cardiac arrest cases, 1.9% of patients]; pulseless supra ventricular tachycardia [28.5% of cardiac arrest cases, 1.1% of patients]; Heart Failure [7% of cardiac arrest cases, 0.2% of patients]; Aorta Arc Rapture [3.5% of cardiac arrest cases, 0.1% of patients]; Tamponade due to pericardial effusion [3.5% of cardiac arrest cases, 0.1% of total patients]; Right Atrium Rupture [3.5% of cardiac arrest cases, 0.1% of patients] were detected after cardiac surgery. Out of 28 cases 7 deaths occurred [25% of cardiac arrest cases, 0.1% of patients]. The most prevalent reason for cardiac arrest during post operative phase was massive bleeding [50%] followed by pulseless supra ventricular tachycardia [28.5%]. Six patients had some morbidity and the remaining 15 patients recovered. There are often multiple contributing factors to a cardiac arrest under cardiac anesthesia, as much a complete systematic assessment of the patient, equipment, and drugs should be completed. We also found that the diagnosis and management of cardiac arrest in association with cardiac anesthesia differs considerably from that encountered elsewhere