Quinoxalinylethylpyridylthioureas (QXPTs) as potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors. Further SAR studies and identification of a novel orally bioavailable hydrazine-based antiviral agent.

Quinoxalinylethylpyridylthioureas (QXPTs) represent a new class of human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) whose prototype is 6-FQXPT (6). Docking studies based on the three-dimensional structure of RT prompted the synthesis of novel heteroarylethylpyridylthioureas which were tested as anti-HIV agents. Several compounds proved to be potent broad-spectrum enzyme inhibitors and significantly inhibited HIV-1 replication in vitro. Their potency depends on the substituents and the nature of the heterocyclic skeleton linked to the ethyl spacer, and structure-activity relationships are discussed in terms of the possible interaction with the RT binding site. Although the new QXPTs analogues show potent antiviral activity, none of the compounds tested overcome the pharmacokinetic disadvantages inherent to ethylpyridylthioureidic antiviral agents, which in general have very low oral bioavailability. Through an integrated effort involving synthesis, docking studies, and biological and pharmacokinetic evaluation, we investigated the structural dependence of the poor bioavailability and rapid clearance within the thioureidic series of antivirals. Replacing the ethylthioureidic moiety with a hydrazine linker led to a new antiviral lead, offering promising pharmacological and pharmacokinetic properties in terms of antiviral activity and oral bioavailability.

A new selective synthesis of the Ile-allo-Thr-Gly tripeptide fragment of lysobactin.

[formula: see text] trans-Aziridine-2-carboxylic acid derivatives are useful intermediates for the synthesis of threonine or allo-threonine through ring expansion and SN2 displacement, respectively. We describe here the preparation of the Ile-allo-Thr-Gly 11 fragment of Lysobactin via the aziridine 9 intermediate.

Duodenal hemangiopericytoma: CT and MRI findings.

Hemangiopericytoma (HPC) is a rare mesenchymal tumor generally occurring in adults and originating from the pericytes. The tumor more commonly affects the soft tissues of the extremities, the pelvis, and the retroperitoneum. We describe the computed tomographic and magnetic resonance appearance of a patient affected by HPC of the duodenum.

[Tridimensional (3D) reconstruction in the osteoarticular area]. / Ricostruzione tridimensionale (3D) in ambito osteoarticolare.

Three-dimensional reconstruction techniques have been used since the development of computed tomography. In skeletal radiology they have been used to better visualize fractures and spatial relationships between fragments in maxillo-facial surgery. Aim of this paper is to illustrate the most important reconstruction techniques and their application in skeletal radiology. Images can be obtained by means of a Spiral CT scanner with the following parameters: collimation/pitch/reconstruction interval 2/1/1. Acquired images are sent to a workstation with a software running on a Window NT platform Vitrea 2.01 (Vital Images, USA) equipped with Volume Rendering algorithm. SSD as well as MPR and curved reformatted reconstruction algorithms is available at the CT console. Three-dimensional reconstruction have been shown to be useful for the diagnosis and for a preoperative planning. Other applications of three-dimensional reconstruction techniques are prosthesis engineering and biomechanic research. 3D images help the communication between radiologist and surgeons. Technical advances in acquisition methods and in reconstruction algorithms are needed to improve image quality and use in skeletal radiology.

Diffusional effects in the steady state kinetics of ubiquinol cytochrome c reductase in bovine heart submitochondrial particles.

The steady-state kinetics of ubiquinol cytochrome c reductase was investigated in submitochondrial particles using ubiquinol-1 as electron donor in media of increasing viscosities obtained by water-polyethylene glycol mixtures. The minimum association rate constant, kmin = kcat/km, for cytochrome c was strongly viscosity dependent, whereas kmin for ubiquinol-1 was only weakly affected by viscosity. It is concluded that the interaction of cytochrome c with the membranous reductase is largely under diffusion control, whereas the oxidation of ubiquinol by the enzyme is not significantly controlled by diffusion in either the aqueous medium or the membrane. The results are compatible with the presence of a diffusion limited step in cytochrome c but not in ubiquinone in mitochondrial electron transfer.

[Shoulder diseases in throwing athletes: radiologic assessment and surgical correlation]. / Patologie della spalla del lanciatore: valutazione radiologica e correlazioni chirurgiche.

Lesions of the shoulder, especially rotator cuff tears and glenoid labrum (SLAP) lesions, are commonly caused by traumatic episodes in athletes such as repeated trauma from throwing. The available radiological methods are MRI, CT and MR arthrography. Twelve athletes suffering from shoulder pain or instability have been studied and then underwent successful treatment in arthroscopy. On the basis of our results and experience, we think that MR, especially with intra-articular injection of contrast medium, is the best examination because it offers an accurate evaluation of both rotator cuff and glenoid labrum. Nevertheless difficulties are often encountered and definitive diagnosis sometime rests on arthroscopic exploration.

[Shoulder instability: diagnostic imaging]. / Instabilità di spalla: diagnostica per immagini.

Shoulder instability is often diagnosed among athletes; two clinical forms are distinguished: anatomical instability, with recurrent luxation of the shoulder, and functional instability, with pain, articular "click" and sensation of instability. Lesions of periarticular soft tissues (capsula, fibrocartilaginous labrum, gleno-humeral ligaments and rotator cuff) are common in both forms, while lesions of bone structures (humeral head and glenoid of scapula) are typical of shoulder with previous dislocation. Purpose of our retrospective study was to verify the value of magnetic resonance (MRI) and computed arthrography (arthro-CT) in diagnosing these lesions in 57 patients suffering from shoulder instability. On the basis of our results and experience we think that in a preoperative evaluation of an unstable shoulder, arthro-CT and arthro-MRI are more accurate because the intra-articular injection of a contrast medium better identifies lesions of capsula, gleno-humeral ligaments and fibrocartilaginous labrum. In other circumstances, such as the study of the shoulder for legal purposes, MRI is preferable because it offers an accurate and global evaluation of periarticular structures.

[Wrist trauma: diagnostic imaging]. / Traumatologia del polso: diagnostica per immagini.

Wrist injury is common throughout life and, although history and physical examination provide important information regarding the type of lesion, a radiological study is essential to determine a specific diagnosis. Conventional radiography plays a central role in the wrist injuries but the diffusion of more sensitive methodics offers new possibilities. Our purpose is to evaluate the role of computed tomography (CT), magnetic resonance (MR) and arthrography in wrist trauma. We retrospectively examined the images of 45 patients with wrist injuries: in every patients a radiological examination in 4 standard projections was executed while in 25, 9 and 11 patients CT,MR and arthrography were performed. On the basis of our findings we think that conventional radiography is often sufficient for diagnosis of bone lesions even if CT sometimes is required to detect subtle fractures. MR has an high sensitivity not only for abnormalities of soft tissues, including interosseous ligaments and triangular fibrocartilage, but also bony abnormalities such as occult fractures and early osteonecrosis. Arthrography still remains the best procedure for evaluating lesions of triangular fibrocartilage and intercarpal ligaments especially in a preoperative phase.

[Femoro-patellar instability: radiologic assessment]. / Instabilità femoro-rotulea: valutazione radiologica.

To propose a simple and reproducible radiological evaluation of the patellofemoral instability that enables the orthopaedic in choosing the best therapy. The radiographs and CT examinations of 55 patients, 38 female and 17 male (range 18-32 years) have been evaluated retrospectively. Twenty-height of them underwent surgical treatment for patellar instability. A radiological protocol which includes conventional radiographs in two projections and a CT examination both in extension, with and without quadriceps contraction, and in flexion at 20 degrees allows to give all the informations one's need for evaluating patellar height and mobility, trochlear dysplasia, valgism of the knee and the degree of excessive lateral position of the anterior tibial tuberosity. It's a simple, quick, accurate and reproducible protocol to do, even with different radiological systems.

[Spiral CT in maxillo-facial trauma]. / Spiral-TC in traumatologia maxillo-facciale.

Fractures of facial skeleton are common in a busy emergency department in often requires careful radiological study before surgical treatment. Radiographic evaluation of facial injuries is especially challenging because the complex facial structure results in a confusing overlapping of densities on the radiograph. Instead Spiral-CT enables obtaining images on different planes so that even subtle or complex fractures may be evaluated in the best way. Moreover, associated lesions of important organs can be diagnosed. Our purpose is to verify the value of Spiral-CT in traumatology of facial skeleton. We have evaluated retrospectively the images of 82 patients admitted for facial trauma. On the basis of our findings we think that conventional radiography should be reserved only for light traumas of superficial structures (nose, zygomatic arch, body of jaw); in the remaining cases Spiral-CT should be the first radiological examination.

[Cervical spine injuries: diagnostic imaging]. / Traumatologia del rachide cervicale: diagnostica per immagini.

In past few years, traumas of cervical spine have increased, chiefly owing to rise of road accidents. Nevertheless, only in a small percentage of cases lesions of cervical spine occur and, in order to reduce many negative radiographs, a careful clinical examination is required. Our purpose is to verify the value of radiology in evaluation of acute trauma of cervical spine and to propose an adequate radiological protocol. In the course of two years (1998-99), 376 patients were admitted in consequence of cervical trauma of different degree of gravity. In all patients, conventional radiographs were obtained, in 93 a computed tomography (CT) examination was executed and only in 18 patients with neurological symptoms a magnetic resonance (MR) was required. Fractures of cervical spine wee identified in 91 cases and in patients in which MR images were obtained, neurological lesions of various severity were diagnosed. On the basis of our results, we think that, in a clinical suspicion of cervical spine lesions, a conventional radiographic study has first to be performed even if often good radiographs aren't obtained for technical difficulties. If doubts persist on conventional radiographs or a fractures has already been diagnosed on radiographs but we want to verify its stability, a CT needs to be performed. MR is required if neurological symptoms are present in order to diagnose lesions of spinal marrow, nerve roots or ligaments.