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Objective: To investigate if markers of exposure to foodborne and orofecal microbes versus airborne viruses are associated with atopy and respiratory allergies., Design: Retrospective case-control study., Participants: 240 atopic cases and 240 non-atopic controls from a population sample of 1659 participants, all Italian male cadets aged 17-24., Setting: Air force school in Caserta, Italy., Main Outcome Measures: Serology for Toxoplasma gondii, Helicobacter pylori, hepatitis A virus, measles, mumps, rubella, chickenpox, cytomegalovirus, and herpes simplex virus type 1; skin sensitisation and IgE antibodies to relevant airborne allergens; total IgE concentration; and diagnosis of allergic asthma or rhinitis., Results: Compared with controls there was a lower prevalence of T gondii (26% v 18%, P=0.027), hepatitis A virus (30% v 16%, P=0.004), and H pylori (18% v 15%, P=0.325) in atopic participants. Adjusted odds ratios of atopy decreased with a gradient of exposure to H pylori, T gondii, and hepatitis A virus (none, odds ratio 1; one, 0. 70; two or three, 0.37; P for trend=0.000045) but not with cumulative exposure to the other viruses. Conversely, total IgE concentration was not independently associated with any infection. Allergic asthma was rare (1/245, 0.4%) and allergic rhinitis infrequent (16/245, 7%) among the participants (245/1659) exposed to at least two orofecal and foodborne infections (H pylori, T gondii, hepatitis A virus)., Conclusion: Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes. Hygiene and a westernised, semisterile diet may facilitate atopy by influencing the overall pattern of commensals and pathogens that stimulate the gut associated lymphoid tissue thus contributing to the epidemic of allergic asthma and rhinitis in developed countries.

Objective: Patients with hypertension tend to have a high prevalence of atherothrombotic accidents. Platelet hyperactivity is frequently associated with hypertension. Because the vascular disease associated with hypertension evolves over the years, we investigated platelet activity parameters in a population of older hypertensive patients with no other risk factors for cardiovascular disease., Participants: We studied 34 older, nonsmoking patients (mean age 74 +/- 5 years) with uncomplicated hypertension before and after the normalization of blood pressure (BP) was achieved with the angiotensin-converting enzyme inhibitor quinapril alone or in combination with the Ca2+ antagonist nifedipine., Measurements: Platelet aggregation, P-selectin (CD62) expression on the platelet surface, serum levels of Interleukin-1beta (IL-1beta) and of Interleukin-6 (IL-6), as well as plasma levels of soluble P-selectin and Endothelin-1 (ET-1), were analyzed., Results: All platelet hyperactivity parameters were reduced significantly with the normalization of BP at the end of antihypertensive drug treatment (systolic/diastolic: 186.2 +/- 2.7/103.4 +/- 1.1 mm Hg vs 135.0 +/- 1.3/85.9 +/- 1.9 mm Hg; P < .001). Those factors more strictly associated with endothelium injury, such as ET-1 and IL-6, did not show variations. A significant correlation (Spearman Rank test) was observed among all platelet function parameters and blood pressure values., Conclusions: This study demonstrated that even in a population of older hypertensive patients with no other risk factor for atherogenic disease, normalization of blood pressure induces a significant reduction of the parameters of enhanced platelet hyperactivity independent of the action exerted, at the platelet level, by the antihypertensive drugs.

U46619 is a potent platelet agonist, its binding to the thromboxane A2 receptor resulting in Gq-binding protein-mediated responses; nevertheless, it is unable to cause platelet aggregation, unless released ADP is present. In this study we demonstrate that Gi activation is the step U46619 lacks to cause platelet aggregation; in fact, when platelets were treated with an ADP scavenger system, the response to U46619 was restored by the addition of epinephrine, which activates platelets via a Gi protein. The concomitant activation of Gi and Gq proteins does not require increased cytosolic calcium to cause aggregation, as assessed by the fact that platelets treated with the intracellular calcium chelator BAPTA were able to respond to U46619 provided ADP or epinephrine was present. Moreover, as the calcium ionophore ionomycin, at low concentrations, potentiated the response to U46619 but not to epinephrine, we may conclude that calcium influx preferentially activates a Gi downstream signalling pathway.

In a suspension of thrombin degranulated platelets (TDP), ADP and epinephrine can induce platelet aggregation, whereas the synthetic agonist of the thromboxane/endoperoxide receptor U46619 causes only shape change. However, U46619 can enhance platelet aggregation induced by ADP and epinephrine. In this paper, we have measured fibrinogen binding in relation to phospholipase C (PLC) activation and calcium mobilization in TDP activates by ADP, epinephrine and U46619. ADP caused fibrinogen binding in TDP but neither activated PLC nor caused a calcium mobilization. The requirement for ADP in inducing exposure of fibrinogen binding sites was not absolute since the combination of epinephrine and U46619 produced an increase in fibrinogen binding. U46619 caused significant PLC activation and cytosolic calcium release but not fibrinogen binding. These results suggest that in TDP the exposure of fibrinogen binding sites, after agonist activation, is independent of both PLC activation and calcium mobilization.