Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: role in restricted conformational mobility and compaction of native state

Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193-7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein's surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.     

Airway stents. Present and future

Tracheobronchial stent insertion is a relatively new technique used to palliate or cure central airways obstruction. When performed by experienced thoracic endoscopists, this procedure is both safe and effective, even if complications of indwelling stents may require repeat endoscopic intervention. Although proven clinically beneficial to many patients, airway prostheses have not yet been the subject of large comparative case studies or randomized controlled investigations. Reports are often experiential and anecdotal. Further research is needed to determine the effects of stenting on survival in patients with malignant airway disease and its degree of success in patients with benign airway strictures. Only then will airway stents truly deserve their place alongside other therapies for tracheobronchial obstruction.     

Paroxysmal atrial fibrillation

Paroxysmal atrial fibrillation is the most frequent of cardiac arrhythmias and its frequency increases with age. Its diagnosis is difficult since the symptoms are often absent or misleading. It is based on electrocardiogram performed during the attack, and this has been made easier by the Holter technique or by sequential recordings triggered by the patient himself. It is only in special cases, when percritical recordings could not be made that intracavitary electrophysiological study is used to obtain indirect arguments in favour of the diagnosis. All heart diseases can be attended by this cardiac rhythm disorder which usually marks an unfavourable turn in the course of the disease, with an increased risk of sudden death in the end. But in most cases the only disorder found is a common arterial hypertension. Atrial fibrillation carries a risk of peripheral, and in particular cerebral, embolism evaluated at 5% per annum. This risk is high in patients with cardiopathy, but it also exists even with a normal heart. The value of anticoagulants has been demonstrated by large controlled studies, but it is important to know that a very strong anticoagulant treatment is unnecessary to reduce the risk of embolism. Only antiarrhythmic agents can maintain the patients in sinus rhythm for as long as possible before the passage to permanent fibrillation. Although no beneficial effect on mortality has been proved, these drugs are indicated for patients who have very marked symptoms or a major cardiopathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related changes in cognitive ERPs of attenuation

The purpose of this article is to deliberate the moral and legal dilemma entailed in the weapon of the labour strike as a pressure tactic on the Israeli Finance Ministry regarding job slots, budgets and, in effect, violating the collective agreement signed by the nurses and impairing patients' treatment, as opposed to refraining from striking and suffering the heavy burden of work, the lack of trained personnel, low wages, and the inability to give patients proper, high quality treatment.