Role of adenoids and adenoiditis in children with allergy and otitis media

Adenoids and/or tonsil inflammation with concomitant obstructive hypertrophy is one of the oldest and most common pediatric problems. Adenoids are a component of Waldeyer’s ring and because of their anatomic position can be relevant in the pathogenesis of otitis media when they are inflamed and/or enlarged. Adenoid pads can create mechanical eustachian tube obstruction. Therefore, in some cases, adenoidectomy may have a role in the clinical management of otitis media with effusion. However, eustachian tube dysfunction related to the adenoids may also have an allergy-related functional component. Allergic inflammation has been described for middle ear effusion, and some studies have reported that mast cells increase and allergic mediators release in adenoids as well. Nasal endoscopy has a key role in confirming a diagnosis of adenoid hypertrophy and/or adenoiditis and in detecting an association between adenoid inflammation/infection and otitis media with effusion, especially during infancy and early childhood.     

Oral factor Xa inhibitors for thromboprophylaxis in major orthopedic surgery: a review

Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a major cause of morbidity and mortality in patients undergoing major orthopedic surgery. Routine thromboprophylaxis has been the standard of care over the last 20 years. Currently available options for the prevention of VTE in major orthopedic surgery include low molecular weight heparins, vitamin K antagonists, and, more recently, the synthetic pentasaccharide fondaparinux. Although effective, all these drugs have several limitations and new oral antithrombotics offering predictable, effective and safe anticoagulation are strongly needed. This overview focuses on the most advanced oral direct inhibitors to factor Xa rivaroxaban, apixaban, LY517717 and YM150; specifically, the results of phase II and III studies and the designs of ongoing clinical trials in patients undergoing elective hip and knee replacement are reviewed.     

In-Line Optimization and Control of an Industrial Freeze-Drying Process for Pharmaceuticals

This paper deals with the in-line optimization and control of the freeze-drying process of pharmaceuticals in vials. The proposed control system, named LyoDriver, uses a mathematical model of the process to calculate the values of the temperature of the heating fluid: the goal is to minimize the time required to get the desired amount of residual water in the dried product, and to maintain product temperature below the maximum allowed value, thus preserving product quality. The values of product temperature and residual ice content, as well as other parameters, are required to perform the calculations: these variables are estimated in-line by means of the Dynamic Parameters Estimation algorithm, an advanced tool based on the pressure rise test, but also other monitoring systems can be used. Two different control algorithms are presented and investigated by means of mathematical simulation and experiments carried out in a small industrial-type apparatus (LyoBeta 25 by Telstar). Results show the effectiveness of LyoDriver in a wide range of operating conditions, even when the process becomes mass-transfer controlled, or when the operating pressure is changed.     

Effects on molecular conformation and anticoagulant activities of 1,6-anhydrosugars at the reducing terminal of antithrombin-binding octasaccharides isolated from low-molecular-weight heparin enoxaparin

Terminal 1,6-anhydro-aminosugars (1,6-anAS) are typical structural moieties of enoxaparin, a low-molecular-weight heparin (LMWH) widely used for prevention and treatment of thrombotic disorders. In the enoxaparin manufacturing process, these modified amino sugars are formed during the β-eliminative cleavage of heparin. To investigate the effect of terminal anAS on antithrombin (AT) binding and on inhibition of factor Xa (FXa), two octasaccharides containing modified AT-binding pentasaccharide sequences were isolated from enoxaparin. The molecular conformation of the octasaccharides terminating with N-sulfo-1,6-anhydro-D-mannosamine and N-sulfo-1,6-anhydro-D-glucosamine, respectively, has been determined both in the absence and presence of AT by NMR experiments and docking simulations. Reduced overall contacts of the terminal anAS residues with the binding region of AT induce a decrease in affinity for AT as well as lower anti-FXa activity. The anti-FXa measured either in buffer or plasma milieu does not show any significant difference, suggesting that the inhibition of anti-FXa remains specific and biologically relevant.     

Microvascular adaptation to growth in rat humeral head

The aim of this work is to investigate the growth of the vasculature in the rat humeral head cartilage after the initial development of the secondary ossification centre until the adult organization. Rats aging from 5 weeks to 12 months were used. Histological observations on humeral heads were implemented with morphometrical analysis. Subsequently, vascular corrosion cast, that permits a three-dimensional observation of the vasculature, were prepared and observed by scanning electron microscopy. In young animals the epiphysis contains thin bone trabeculae and most of the epiphysis is occupied by bone marrow spaces. With age, the bone trabeculae progressively enlarge up to double their thickness. The percentage of bone tissue increases from 33.6 to 58.6% of the entire epiphysis, while the bone marrow spaces tend to increase very little in their mean dimension. Vascular corrosion casts show that the epiphyseal microcirculation is well distinguished from that of the diaphysis, and arises from the vessels present in the capsule and the periosteal networks. In young animals the only capillaries are bone marrow sinusoids and few subchondral capillaries. In adult animals small vessels run between the clusters of sinusoids forming the trabecular circulation. Capillary sprouts from sinusoids are always observed both in the young and adult animals. Thus, in adult rats different proper microcirculatory districts can be distinguished in the epiphysis: (a) the sinusoidal network, that supplies the hematopoiesis of the bone marrow and the adjacent osteogenic tissue; (b) the bone tissue microcirculation, limited to small vessels that supply the metabolism and the remodelling of the bone tissue. The reported microvascular organization and its adaptation to the epiphyseal growth represent the morphological basis for understanding the reciprocal interaction among the different tissues in developing and adult rat epiphysis.