Component resolved diagnosis by recombinant allergens in patients with allergies to inhalants.

Molecular characterization of IgE reactivity of specific individual components of allergenic extracts is now possible due to the technology of recombinant allergens derived from studies of molecular biology of allergic pathology. The identification of the immunoreactivity to single allergenic components in allergic subjects allows to specifically define her/his allergic profile and obtain the so-termed Component Resolved Diagnosis (CRD). Molecular allergens can be classified into those that induce the respiratory allergic reactivity and those that identify the food-related allergic pathology. It is also essential to identify those molecular allergens whose immunoreactivity is able to connect the two clinical conditions: respiratory symptoms and food allergy symptoms. The present study was conducted on 50 patients with a clinical history of hypersensitivity to pollen and/or allergy and positivity to Skin Prick Test. The sera were analyzed in our laboratories and the panel of recombinant allergens was applied in the case of positivity of the specific IgE. Of the 50 patients enrolled, 31 were selected as positive to 4 main pan-allergen Bet v1, Par j2, Art v1 and Phl p1; among these, 14 subjects showed one allergen-specific IgE towards natural extracts of tested foods even in absence of clinical history. CRD allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in: a) resolving genuine vs cross-reactive sensitization in poly-sensitized patients, b) assessing, in selected cases, the risk of severe, systemic vs mild, local reactions in food allergy, and c) identifying patients and triggering allergens for specific immunotherapy (ITS). In light of our results, we believe that the transition from a diagnostic based on the use of allergenic extracts to another one based on the use of single allergenic molecules that is able to define the specific allergenic profile of each patient, seems to be able to revolutionize the allergy diagnosis.

Human cardiac multipotent adult stem cells in 3D matrix: new approach of tissue engineering in cardiac regeneration post-infarction.

Myocardial infarction is the leading cause of morbidity and mortality in developed countries. It causes a left ventricular dysfunction, mainly due to the loss of functional tissue, resulting in heart failure. New therapies are being developed, using a tissue engineering approach, with the ultimate goal of restoring cardiac function by regenerating and repairing the damaged myocardium. In the present study we investigated the behaviour of a specific population of c-kit positive human cardiac stem cells, called Multipotent Adult Stem Cells (MASCs), grown within three-dimensional collagen scaffolds (3D), to establish whether they could be used in post-infarction cardiac regeneration. We also evaluated the expression levels of the Granulocyte Macrophage-Colony Stimulating Factor Receptor (GM-CSFR) and endoglin, a component of the Transforming Growth Factor beta (TGF-ß) receptor complex. Finally, we also evaluated the expression of the α2ß1integrin. MASCs cultured within 3D collagen matrices are able to proliferate and migrate even in the absence of chemotactic agents and express high levels of factors involved in cell proliferation and migration, such as GM-CSFRα chain and integrins. They therefore represent a promising approach to tissue engineering aimed to restore cardiac function. Our results also suggest a role of GM-CSF in cell proliferation, while TGF-ß does not seem to be relevant.

Vitamin D receptor polymorphisms as tool for early screening of severe bone loss in women patients with rheumatoid arthritis.

OBJECTIVE: Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that leads to local and systemic arthritis and bone loss. Exploring genetic markers of candidate genes in osteoporosis and inflammatory cytokine genes could be a useful tool for the early identification of bone loss and fracture risk in RA patients. The target of this study is the evaluation and correlation between of Single Nucleotide Polymorphisms (SNPs) of Vitamin D Receptor (VDR) and possible effects on bone loss in RA. PATIENTS AND METHODS: 40 Caucasian patients with RA (26 of them with a severe bone loss) and 40 healthy donors as control samples were genotyped for the VDR SNPs (called BsmI, ApaI, TaqI and FokI). The detection method is based on Restriction Fragment Length Polymorphism (RFLP). RESULTS: Genotyping profile shown no difference between RA patients and controls. Only VDR-TaqI genotype (TT vs. tt) seem to influence the bone density in females, but not in males. The mean differences of Bone Mass Density (BMD) at the lumbar spine in RA women with the tt allele were 4.7% compared to 0.1% in women with the TT allele (p < 0.05). CONCLUSIONS: The results of these studies support an association between specific VDR alleles and bone loss in RA. The TaqI t and BsmI B alleles were associated with an accelerated bone loss in RA, but not with a focal bone loss. These effects of VDR genotypes and vitamin D supplementation are not unexpected, given that the central pathological feature in RA is bone and joint destruction. The VDR SNPs genotyping should be a useful tool to screen early women RA patients with the bone loss.

Differential expression of a truncated form of the urokinase-type plasminogen-activator receptor in normal and tumor thyroid cells.

We studied the urokinase-type plasminogen activator (uPA) receptor (uPA-R) in normal and neoplastic human thyroid cells. It has recently been shown that cleaved forms of uPA-R display an extremely strong chemotactic activity. Normal human thyroid TAD-2 cells express the intact form of the uPA-R and a truncated form lacking the uPA-binding domain on their surface, in a similar manner to tumor thyroid cell lines. However, in tumor thyroid cell lines, the amount of the truncated form is variable: high in papillary carcinoma cells, very low in follicular carcinoma cells, and not detectable in anaplastic carcinoma cells. Similar studies on primary cell cultures confirm the presence of the truncated form of uPA-R in normal and in papillary carcinoma cells and its partial or total loss in follicular carcinoma cells. The presence of truncated uPA-R correlates to uPA secretion, except in papillary carcinoma cells, which express the truncated form of uPA-R but do not release uPA. uPA-R is also able to act as an adhesion receptor by binding vitronectin (VTN) and interacting with integrins. We observe that removal of uPA-R from the surface of normal thyroid and anaplastic carcinoma cells by phosphatidylinositol-specific phospholipase C or treatment with anti-uPA-R antibodies decreases the adhesion of both cell types to VTN and, less efficiently, to fibronectin or collagen. On the other hand, uPA treatment strongly increases the adhesion of anaplastic carcinoma cells specifically to VTN.

Evaluation of pefloxacin activity against recent clinical isolates.

The in-vitro antibacterial activity of pefloxacin, a new quinolone carboxylic acid, was tested against 1140 bacterial strains, recently clinically isolated, by measuring the minimum inhibitory concentrations. Comparisons were made with other quinolones (enoxacin, norfloxacin, flumekin, oxolinic acid, pipemidic acid) and other drugs (piperacillin, cefotaxime, ceftazidime, gentamicin, tobramycin, amikacin) widely used for the treatment of bacterial infections. Pefloxacin was very active against the tested species and was the most active drug against all the bacterial strains, with a geometric mean of MICs, a MIC 50 and MIC 90 of 0.27, 0.12 and 4 microg/ml respectively.

Evaluation of ciprofloxacin's activity against recent clinical isolates.

The in vitro antibacterial activity of ciprofloxacin, a new quinoline carboxylic acid, was tested against 1671 recently clinically isolated bacterial strains, by measuring the minimum inhibitory concentrations (MIC). Comparisons were made with other quinolones: nalidixic acid, norfloxacin, and other drugs: piperacillin, cefoxitin, cefotetan, ceftazidime, tobramycin, rifampin, tetracycline, chloramphenicol. Ciprofloxacin was very active against the tested species and was the most active drug against all the bacterial strains, with a geometric mean, a MIC50 and MIC90 of 0.27, 0.12 and 2 micrograms/ml, respectively.

[Monotherapy, empirical and targetted, with imipenem-cilastatin in sepsis of bacterial origin]. / La monoterapia, empirica e mirata, con imipenem-cilastatina nelle sepsi ad eziologia batterica.

The authors describe an open study in 22 patients with febrile conditions of unknown origin who were treated with imipenem-cilastatin while waiting for routine laboratory and culture tests. These were done immediately at the patients' entry into hospital, after which imipenem-cilastatin treatment was started immediately, and was subsequently confirmed by the isolates and culture tests. The drug was found to be active and to eradicate the responsible organism in all cases. In addition, it was found to be easy to handle and not to give rise to side-effects or changes in laboratory tests.

Evaluation of in vitro activity of teicoplanin against recent clinical isolates.

The in vitro antibacterial activity of teicoplanin, a new glycopeptide antibiotic, previously named teichomycin A2, has been compared to that of five other chemoantibiotics: netilmicin, clindamycin, rifampicin, enoxacin and vancomycin. The minimum inhibitory concentration (MIC) values against 588 gram-positive strains, 561 facultative aerobes and 27 anaerobes, recently isolated from clinical specimens, were evaluated. Teicoplanin showed the highest activity against all the tested strains, with a geometrical mean of the MICs (GMM), a MIC50 and MIC90 of 0.123, 0.12 and 0.5 micrograms/ml respectively.

[Bactericidal and potent antiadhesive activity of sulbenicillin]. / Studio dell'attivita battericida di sulbenicillina e del suo potere antiaderente.

Sulbenicillin, a wide broad spectrum penicillin, is active against a lot of gram positive and gram negative bacteria. The AA. studied the activity of this molecule against urinary infections causing germs, by evaluating two parameters: his antiadhesive capability and the Killing curves, in comparison with mezlocillin and piperacillin. An inhibition in adhesive capability of test-germs, due to sulbenicillin was obtained. Furthermore, resulting Killing curves showed more rapidity in action for sulbenicillin than for the two others molecules, versus resistant germs, like P. aeruginosa and S. faecalis.

[Biomechanics of vertebral segments. Clinical and prognostical interpretations (author's transl)]. / Biomechanisches Verhalten der Wirbelsäule-Segmente. Klinische und prognostische Bedeutung

The authors propose a new model to estimate the forces of the intrinsic equilibrium of the segment. Based on the theory of the so-called transient pole, it became possible to describe the momentary movement of an angle relative to its neighbour and to define the way of the intrinsic equilibrium. This transient pole fixes the centre of rotation around which the upper angle moves relative to the lower vertebral body. Normal and pathological cases can be diagnosed at once by use of a special röntgenological appliance in connection with the statistical experience. It becomes possible to calculate the forces and movements acting on a segment.

[Can the human posture be explained by biomechanics? (author's transl)]. / Biomechanische Aspekte der menschlichen Haltung

Up to now, lacking a bio-mechanical model, human posture has only been examined morphologically, although the physics of posture respond to simple laws. With the help of a physical model, based on the hypothesis of a minimal rotating movement of the trunk and head from the spine, this report gives a description of a normal posture. The model can be extended mathematically to establish a computer simulation of each case examined by X-ray, showing which posture would use the smallest amount of ligamentary and muscular force. The above bio-mechanical analyses of the spine as a whole is being further examined and improved mathematically.

[Contribution toward determining the inner equilibrium of the spinal column (pivotal point as temporary pole) (author's transl)]. / Beitrag zur Bestimmung des inneren Gleichgewichtes der Wirbelsäule (Der Drehpunkt als Momentanpol)

The estimation of the centre of rotation of a spine segment can be shown as a transient pole, which follows the polar curve of the movement of the upper segment of the spine, relative to the lower one. With the help of X-ray, it is possible to evaluate two separate positions of the pole, from the normal position to the medium flexion and from the medium to the extreme flexion of the lumbal segment. Based on these expected values, as well as their intervals, pathological cases can be recognized, which is also shown in an example.

[Biomechanic contribution to measurement of power and action of neck muscles (author's transl)]. / Biomechanischer Beitrag zur Berechnung der Kräfte der Halsmuskulatur und deren Wirkung

The position of the head depends on the function of the neck-muscles. Once the power of stabilization has been exhausted, the ligaments, particularly the superficial posterior, are stressed. A mathematical model has been developed for measuring the power of the muscles. This enables us to find out when and to which degree stress on the ligaments contributes to stabilization.