Large-Volume Crystalloid Fluid Is Associated with Increased Hyaluronan Shedding and Inflammation in a Canine Hemorrhagic Shock Model.

Shedding of the endothelial glycocalyx precedes leukocyte activation and adherence in acute inflammation. Rapid administration of crystalloid or colloid fluids for treating hemorrhagic shock may cause endothelial glycocalyx shedding, thereby increasing inflammation. This study aimed to compare the effect of different fluid treatments in a canine shock model on glycocalyx biomarker, hyaluronan, and inflammatory biomarkers. Greyhound dogs under general anesthesia subject to hemorrhage for 60 min were given 20 mL kg-1 of either fresh whole blood (FWB), hydroxyethyl starch (HES) 130/0.4, 4% succinylated gelatin (GELO), or 80 mL kg-1 of isotonic crystalloid (CRYST) over 20 min (n = 6 per group). Plasma biomarkers hyaluronan, interleukin (IL) 6, 8, 10, tumor necrosis factor-α, monocyte chemoattractant protein-1, keratinocyte chemokine-like, and atrial natriuretic peptide were measured at baseline, end of hemorrhage (Shock), end of fluid administration (T20), and then 40 (T60), 100 (T120), and 160 (T180) minutes later. Biomarker concentrations were compared between groups using the Kruskal-Wallis test or Fisher's exact test (measurable versus unmeasurable) (significance set at P < 0.05). Hyaluronan concentration peaked early in the CRYST group at T20, compared to HES (P = 0.005) and GELO (P = 0.018), and later in the GELO group at T60, compared to FWB (P < 0.001). The CRYST group had significantly more samples with measurable IL6 at T180 (P = 0.015), compared to GELO, and IL10 at T60, T120, and T180 (all P = 0.015), compared to FWB. There were no significant differences in other biomarker concentrations. In conclusion, rapid large-volume crystalloid administered for hemorrhagic shock was associated with increased hyaluronan and a greater inflammatory response.

Neutrophil activation during acute human anaphylaxis: analysis of MPO and sCD62L.

BACKGROUND: The mechanisms involved in the amplification of the mast cell response during anaphylaxis are unclear. Mouse models of anaphylaxis demonstrate the critical involvement of neutrophils. These innate immune cells are highly abundant in peripheral blood and can be rapidly activated to trigger both local and systemic inflammation. OBJECTIVE: To investigate neutrophil activation in peripheral blood during acute human anaphylaxis. METHODS: Patients presenting to the emergency department with anaphylaxis underwent blood sampling upon enrolment and at up to three subsequent time-points. Traditional anaphylaxis biomarkers, histamine and mast cell tryptase, were measured by ELISA and ImmunoCAP, respectively. Plasma myeloperoxidase concentrations were measured by ELISA, serum soluble CD62L concentrations by cytometric bead array, and both compared to healthy controls. RESULTS: In 72 patients, 37 (51%) had severe anaphylaxis, 33 (60%) were histamine positive, and 47 (70%) were mast cell tryptase positive. At enrolment, myeloperoxidase concentrations were 2.9- (95% CI: 1.3, 6.5) and 5.0- (95% CI: 2.4, 10.5) fold higher in moderate and severe patients, respectively, compared with healthy controls, and remained stable over the first 5 h following symptom onset. At enrolment, soluble CD62L was 29% (95% CI: 19, 38) and 31% (95% CI: 22, 40) lower in moderate and severe patients, respectively, than healthy controls, and was stable over the first 5 h. There were no associations between myeloperoxidase or soluble CD62L concentrations and either histamine or mast cell tryptase concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: These results provide compelling evidence for the involvement of neutrophils during acute human anaphylaxis, suggesting they are activated early in the reaction, regardless of mast cell activation. This important finding increases our understanding of the basic mechanisms of anaphylaxis, a necessary precursor to improving treatment and prevention.

The influence of selective grinding on the thickness discrimination threshold of patients wearing complete dentures.

The influence of selective grinding on the ability of patients wearing complete dentures to discriminate thicknesses occlusally was evaluated. The study included two groups of white Caucasian patients, matched for age, sex and duration of edentulism; 12 wearing traditional complete dentures and 12 wearing maxillary complete denture and mandibular implant-retained overdenture (MIR-OVD). The ability to discriminate thickness was evaluated before and after selective grinding. In both groups, sensitivity improved after selective grinding. Subjects wearing MIR-OVD showed a better ability to discriminate thickness than those rehabilitated with traditional complete dentures. The thickness discrimination threshold might be a suitable method to evaluate complete dentures fit.

Low-dose orally administered type I interferon reduces splenic B cell numbers in mice.

The beneficial effects of low-dose orally administered type I interferon (LDOA IFN) have been demonstrated in various animal models of disease and in some human clinical trials. The mechanisms by which LDOA IFN therapy has its effects, however, remain to be established. In the present study, groups of mice were administered 10 IU murine IFN-alpha/beta (MuIFN-alpha/beta) orally for 7 days. Spleens were then collected and analyzed. No differences were detected between the spleen weights of treated mice compared with controls, although reductions in total splenic white blood cell (WBC) number ranging from 15.5% to 35% were observed. Further analysis showed this reduction to be largely restricted to the B cell population, with only minor reductions in CD4(+) or CD8(+) populations being detected. Dose-response studies showed the WBC loss from the spleen to be optimal at 1 IU MuIFN-alpha/beta, whereas both higher and lower doses showed less significant effects. Time course studies show these effects had developed after 2 days of treatment. It is hypothesized that this observed WBC movement from the spleen is part of the mechanism of action of LDOA IFN.

Seven days of low-dose orally administered murine type I interferon does not cause priming in vivo.

In vivo, low-dose orally administered type I interferon (LDOA IFN) therapy has been shown to provide beneficial effects in a number of diseases. These diseases vary in nature (viral, autoimmune, and neoplastic), yet LDOA IFN therapy is able to provide effective treatment. Despite the growing knowledge of the efficacy of such treatment and ongoing human clinical trials, the mechanism by which LDOA IFN acts remains largely unknown. In this study, we examined the phenomenon known as "priming" as a potential mechanism by which LDOA IFN effects may be mediated. Priming is a phenomenon in which pretreatment of cells or entire organisms with type I IFN causes significantly enhanced IFN production after induction of the endogenous IFN system by virus or polyI:C. This phenomenon of priming has been exploited in commercial industry for the mass production of type I IFN for medical and research use. It was found that LDOA IFN treatment did not cause priming in vivo.

Efficacy of low-dose oral use of type I interferon in cytomegalovirus infections in vivo.

Oral administration of type I interferons (IFNs; murine IFN-alpha and IFN-beta) reduces early replication of murine cytomegalovirus (MCMV) in both the spleen and liver of MCMV-infected BALB/c mice. Examination of a range of doses of IFN (1 to 1000 IU) showed that 10 IU administered daily for 1 week prior to virus infection was optimal for inhibition of MCMV replication. Furthermore, low-dose orally administered IFN (10 IU/day) was effective in mice challenged with lethal and sublethal virus inocula. The antiviral efficacy of low-dose orally administered IFN was not restricted by either the route of virus inoculation or the mouse genotype. Analysis by immunohistochemistry of IFN-alpha receptor-bearing cells of the gastrointestinal tract revealed predominant staining of perivascular smooth muscle and the lamina propria of the anterior tongue, small intestine and rectum. These tissues, dense in IFN-alpha receptor-bearing cells, are likely to be the sites of interaction of the orally administered IFNs with the mucosal immune system. In conclusion, we propose that low-dose oral use of type I IFN therapy may have broad applications in the treatment of CMV infections.

[Acute accidental poisoning by mercury vapors in the home environment]. / Intossicazione acuta accidentale da vapori di mercurio in ambiente domestico.

The authors report 2 cases of acute mercury intoxication due to accidental breakage of barometer on to a lit gas ring. Within 24-48 hours the subjects developed neurological, gastrointestinal and dermatological symptoms. A 24-hour urine sample contained 600 and 400 micrograms of mercury per liter respectively (reference value 0.1-6.9 micrograms/L); blood concentration of mercury was 130 and 100 micrograms per liter (reference value 1.7-9.9 micrograms/L). The patients were treated with penicillamine and daily excretion of mercury was monitored. The residual sources of pollution in the kitchen were identified and bonificated.