Molecular simplification of lipid A structure: TLR4-modulating cationic and anionic amphiphiles

A growing body of data suggests that therapies based on Toll-like receptors (TLR) targeting, in particular TLR4, holds promise in curing autoimmune and inflammatory pathologies still lacking specific treatment, included several rare diseases. While TLR4 activators (agonists) have already found successful clinical application as vaccine adjuvants, the use of TLR4 blockers (antagonists) as antisepsis agents or as agents against inflammatory diseases (including arthritis, multiple sclerosis, neuroinflammations) and cancer is still at a preclinical phase of development. This minireview focuses on recent achievements on the development of TLR4 modulators based on lipid A structure simplification, in particular on compounds having disaccharide or monosaccharide structures. As the TLR4 activity of natural TLR4 ligands (lipopolysaccharide, LPS and its biologically active part, the lipid A) depends on both the structure of endotoxin aggregates in solution and on single-molecule interaction with MD-2 and CD14 receptors, the rational design of TLR4 modulators should in principle take into account both these factors. In the light of the most recent advances in the field, in this minireview we discuss the structure–activity relationship in simplified lipid A analogs, with cationic or anionic amphiphilic structures.     

Decision trees based on automatic learning and their use in cardiology

Computerized information systems, especially decision support systems, have become an increasingly important role in medical applications, particularly in those where important decision must be made effectively and reliably. But the possibility of using computers in medical decision making is limited by many difficulties, including the complexity of conventional computer languages, methodologies and tools. Thus a conceptual simple decision making model with the possibility of automating learning should be used. In this paper we introduce a cardiological knowledge-based system based on the decision tree approach supporting the mitral valve prolapse determination. Prolapse is defined as the displacement of a bodily part from its normal position. The term mitral valve prolaps (PMV), therefore, implies that the mitral leaflets are displaced relative to some structure, generally taken to be the mitral annulus. The implications of the PMV are the following: disturbed normal laminar blood flow, turbulence of the blood flow, injury of the chordae tendinae, the possibility of thrombus's composition, bacterial endocarditis, and finally hemodynamic changes defined as mitral insufficiency and mitral regurgitation. Uncertainty persists about how it should be diagnosed and about its clinical importance. It is our deep belief that the echocardiography enables properly trained experts armed with proper criteria to evaluate PMV almost 100%. But unfortunately, there are some problems concerned with the use of echocardiography. In that manner we have decided to start a research project aimed at finding new criteria and enabling the general practitioner to evaluate PMV using conventional methods and to select potential patients from the general population. To empower one to perform needed activities we have developed a computer tool called ROSE (computeRised prOlaps Syndrom dEtermination) based on algorithms of automatic learning. This tool supports the definition of new criteria and the selection of potential PMV-patients.     

Physiologic responses to loud tones in Israeli patients with posttraumatic stress disorder.

Orbicularis oculi (eye blink) electromyogram, skin conductance, and heart rate responses to 15 consecutive 95-dB, 500-millisecond, 1000-Hz tones with 0-millisecond rise and fall times were measured in 14 patients with posttraumatic stress disorder, 14 patients with other anxiety disorders, 15 mentally healthy subjects with past traumatic experiences, and 19 mentally healthy subjects with no trauma history. The patients with posttraumatic stress disorder showed significantly larger skin conductance and heart rate responses and a trend toward larger electromyogram responses to the tones than every other group. These effects were not explained by subjective anxiety, resting physiologic arousal, physiologic arousal preceding the tone trials, or initial physiologic responsivity. The group with posttraumatic stress disorder was the only one that failed to show habituation of skin conductance responses.     

Somatosensory evoked potential monitoring during intracranial surgery

In the neurosurgical approach to intracranial aneurysms which are often accompanied by arterial spasm and cortical ischaemia, monitoring procedures aim to obtain useful information on cerebral function. SEPs evoked by stimulation of the median nerve at the wrist and of the tibial nerve at the medial malleolus were registered in 45 patients with intracranial aneurysms during neurosurgical procedures. Our results show SEP abnormalities during different stages of neurosurgical procedures in 36 patients out of the monitored 45. Significant abnormalities of SEPs with respect to the control group were decrease of the amplitude of N 20-P 25 complex, lengthening of the absolute latency of the waves N 20- and P 25 and lengthening of the central conduction time (CCT) (N 13-N 20). The greatest SEP abnormalities were registered during the neurosurgical approach to aneurysm and during the clipping procedure. However, the changes were reversible in the majority of the patients. The aim of this paper was to focus on early detection of some cerebral function disturbances during the neurosurgical procedure as well as the prevention of possible brain damage.     

Arthroscopy and microfracture technique in the treatment of osteochondritis dissecans of the humeral capitellum: report of three adolescent gymnasts

The aim of this paper is to report on three cases of symptomatic osteochondritis dissecans of the humeral capitellum in adolescent gymnasts, two females and one male. In all the cases arthroscopic surgery was performed. During arthroscopy, loose osteochondral fragments were removed, the defect was debrided and microfractures were performed. All the three patients regained the full range of motion of the affected elbow, and returned to the high-level gymnastics within a period of 5 months. At 12 months follow-up, all the three patients remained symptomless and were participating in high-level gymnastics. A combination of arthroscopy and the microfracture technique is a reliable method with excellent short-term results in the treatment of the osteochondritis dissecans of the elbow.