Assessment of tetanus immunity status by tetanus quick stick and anamnesis: a prospective double blind study.

BACKGROUND: In patients with wounds admitted to Emergency Departments (ED) acquiring tetanus vaccination history by interview is very unreliable. Protected patients may receive unnecessary prophylaxis and unprotected nothing. Aim of the study was to evaluate tetanus immunity status comparing the traditional anamnestic method with the Tetanus Quick Stick (TQS), a rapid immunochromatographic test. METHODS: A double-blind prospective study was carried out in the ED of the 1,000 bed teaching hospital Umberto I in Rome. Adult patients (≥18) with wounds attending at the ED were randomly included. Tetanus immunity status was evaluated by healthcare workers (HCWs) comparing the TQS test with the anamnesis. TQS test was performed by a trained HCW and afterwards the anamnesis about tetanus immunity status was collected by another HCW unaware of the TQS result. Also cost analysis was carried out. RESULTS: Overall 400 patients (242 males and 158 females) were included, mean age was 46.7 ± 20.2 years (median 44 range 18 - 109), 304 (76.0%) were italians and 96 foreigners (24.0%). Overall, 209 (52.2%) resulted TQS +, and protective immunity level was associated to lower mean age (40.1 ± 16.8 vs 53.8 ± 21,1; p<0,01). Using the anamnestic method 336 (84.0%) patients resulted "unprotected", 52 (13.0%) "partially unprotected" and 12 (3.0%) "completely protected". TQS test results showed that 154 (45.8%) out of 336 "unprotected" and 45 (86.5%) out of 52 "partially unprotected" actually had a protective antibody level. Finally two (16.7%) out of 12 "completely protected" group presented a non protective antibody level. Following only the anamnestic method 201 (50.0%) patients would have received some inappropriate treatment. Adopting TQS test in all patients would also be cost-effective saving € 1.95/patient. As tetanus immunity is inversely related to age, for <51 years old patients unnecessary treatment would have been avoided in 57.1% of patients, with a mean reduction per patient of € 7.50/patient with the TQS vs. € 12.69/patient without. CONCLUSIONS: The study showed that tetanus protective immunity prevalence among adult patients attending our ED is about 50% and is mainly influenced by class age. TQS use allowed to reduce drastically inappropriate tetanus vaccine and immunoglobulins booster treatment. Also TQS use reduced costs.

Neutrophils recruited by CXCR1/2 signalling mediate post-incisional pain.

BACKGROUND: Neutrophil recruitment mediated by the CXCL1/KC chemokine and its receptors CXCR1/CXCR2 plays a critical role in inflammatory diseases. Recently, neutrophil migration and activation triggered by CXCL1-CXCR1/2 signalling was implicated in inflammatory nociception; however, their role in post-surgical pain has not been elucidated. In this study, we addressed the function of neutrophils in the genesis of post-incisional pain in an experimental model of post-surgical pain. METHODS: Mechanical hyperalgesia was determined with an electronic von Frey test in a mouse hindpaw incisional model. Neutrophil accumulation and the level of CXCL1/KC in the plantar tissue were determined by myeloperoxidase activity assay and enzyme-linked immunosorbent assay, respectively. RESULTS: An incision in the mouse hindpaw produces long-lasting mechanical hyperalgesia that persists for at least 72 h after surgery. Following surgery, there was an increase in both neutrophil accumulation and the CXCL1/KC level in the incised paws. The depletion of the mouse neutrophils by vinblastine sulphate or anti-neutrophil antibody treatments reduced the mechanical hyperalgesia after paw incision. Furthermore, the treatment of mice with ladarixin, an orally acting CXCR1/2 antagonist, also reduced both the mechanical hyperalgesia and the infiltration of neutrophils in the incised paws. CONCLUSION: In conclusion, it appears that after surgical processes, neutrophils are recruited by CXCL1-CXCR1/2 signalling and participate in the cascade of events, leading to mechanical hyperalgesia. These results suggest that blocking neutrophil migration through the inhibition of CXCL1-CXCR1/2 signalling might be a target to control post-surgical pain.

Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2 non-competitive allosteric inhibitor.

BACKGROUND AND PURPOSE: DF 2156A is a new dual inhibitor of IL-8 receptors CXCR1 and CXCR2 with an optimal pharmacokinetic profile. We characterized its binding mode, molecular mechanism of action and selectivity, and evaluated its therapeutic potential. EXPERIMENTAL APPROACH: The binding mode, molecular mechanism of action and selectivity were investigated using chemotaxis of L1.2 transfectants and human leucocytes, in addition to radioligand and [(35) S]-GTPγS binding approaches. The therapeutic potential of DF 2156A was evaluated in acute (liver ischaemia and reperfusion) and chronic (sponge-induced angiogenesis) experimental models of inflammation. KEY RESULTS: A network of polar interactions stabilized by a direct ionic bond between DF 2156A and Lys(99) on CXCR1 and the non-conserved residue Asp(293) on CXCR2 are the key determinants of DF 2156A binding. DF 2156A acted as a non-competitive allosteric inhibitor blocking the signal transduction leading to chemotaxis without altering the binding affinity of natural ligands. DF 2156A effectively and selectively inhibited CXCR1/CXCR2-mediated chemotaxis of L1.2 transfectants and leucocytes. In a murine model of sponge-induced angiogenesis, DF 2156A reduced leucocyte influx, TNF-α production and neovessel formation. In vitro, DF 2156A prevented proliferation, migration and capillary-like organization of HUVECs in response to human IL-8. In a rat model of liver ischaemia and reperfusion (I/R) injury, DF 2156A decreased PMN and monocyte-macrophage infiltration and associated hepatocellular injury. CONCLUSION AND IMPLICATIONS: DF 2156A is a non-competitive allosteric inhibitor of both IL-8 receptors CXCR1 and CXCR2. It prevented experimental angiogenesis and hepatic I/R injury in vivo and, therefore, has therapeutic potential for acute and chronic inflammatory diseases.

Targeting C5a: recent advances in drug discovery.

Activation of complement via the innate and adaptive immune system is vital to the body's defences in fighting infections. Unregulated complement activation is likely to play a crucial role in the pathogenesis of several diseases including psoriasis, adult (acute) respiratory distress syndrome (ARDS), bullous pemphigoid (BP), rheumatoid arthritis (RA) and ischemia-reperfusion (I/R) injury. The 74 amino acid peptide C5a is released after complement activation at sites of inflammation and is a potent chemoattractant for neutrophils, basophils, eosinophils, leukocytes, monocytes and macrophages. Recombinant proteins and humanized anti-C5 antibodies have been recently developed for blocking specific proteins of the complement system bringing renewed attention towards complement inhibition. Pharmacological studies have been highlighting the complement fragment C5a as an interesting target for the management of complement mediated diseases. Specific inhibition of C5a biological activity could gain therapeutic benefit without affecting the protective immune response. In the last few years several peptide and non-peptide antagonists of C5a have been discovered and tested in relevant pharmacological models; the availability of orally active compounds is rapidly helping to delineate the precise role of C5a in immunoinflammatory disorders. Moreover, mutagenesis data for the C5a/C5a receptor (C5aR) couple make C5aR a valuable model for mechanistic studies of peptidergic G-protein coupled receptors (GPCRs). The aim of this review is to outline the recent advances in C5a inhibition, especially highlighting the value of a multidisciplinary integrated approach in drug discovery.

Results of the anatomic cementless prosthesis with different types of hydroxyapatite coating.

This study evaluates the clinical and radiographic results and the bone-implant osteointegration obtained with the Anatomic (Zimmer, Warsaw, Ind) cementless total hip prosthesis using three different types of surface coating. Two hundred twenty-seven patients underwent total hip arthroplasty using the Anatomic prosthesis. Patients were divided into groups based on the type of surface coating: in group A (69 patients), prostheses were uncoated; in group B (90 patients), the metaphyseal region of the prostheses was coated with calcicoat (a mixture of hydroxyapatite and tricalcium phosphate) (Zimmer); and in group C (68 patients), the fiber mesh and proximal stem of the prostheses were coated with calcicoat. Prostheses coated with calcicoat yielded better clinical and radiographic results than uncoated prostheses, especially in regard to thigh pain. No significant difference was observed between groups B and C. These results obtained with the Anatomic prosthesis are promising and encourage the use of implants coated with calcicoat.

Histochemical characterization of the naso-labial glands of two species of ruminants (Ovis aries and Bos taurus).

The bovine and ovine naso-labial glands have been examined. In both species these glands are multilobular tubulo-acinar, but the cells of secretory units display differences regarding nuclear shape and location, RER arrangement and secretion pattern. In this paper, histochemical characterization of naso-labial gland secretion was performed using the periodic acid Schiff reaction (PAS), the Alcian blue staining (AB) at pH's ranging between 1.7 and 2.5, the Alcian blue-high iron diamine (HID-AB) method, an immunohistochemical staining for muramidase at the light microscopic level and the periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) technique at the electron microscopic level. In bovines the secretion is composed of glycoproteins, which are reactive to PAS, but not to Alcian blue staining. In ovines, a large quantity of acidic polysaccharides in association with a small quantity of sulfomucins has been found. Ultrastructural and cytochemical observations show that secretory granules do not have a homogeneous structure. They appear to be formed of a meshwork stained positively with the PA-TCH-SP method immersed in a light background. The particular morphological features of the naso-labial glands and their histochemical features suggest that these glands can be classified as sero-mucous in bovines and mucous in ovines.