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alpha-Calcitonin gene-related peptide (alphaCGRP) is a pleiotropic neuropeptide implicated in a variety of physiological processes. To better understand the biological functions of alphaCGRP, we developed an alphaCGRP-null mouse model using a gene targeting approach. Recordings of mean arterial pressure (MAP) and heart rate (HR) showed that basal MAP and HR were significantly higher in both anesthetized and conscious, unrestrained alphaCGRP-null mice than in corresponding wild-type mice. The elevated MAP in alphaCGRP-null mice was shown to be the result of elevated peripheral vascular resistance by alpha-adrenergic blockade with prazosin and by transthoracic echocardiogram, which revealed no significant differences between alphaCGRP-null and wild-type mice in the stroke volume, fractional shortening, and ejection fraction. Moreover, evaluation of autonomic nervous activity by measuring HR after pretreatment of atropine and/or atenolol and by analyzing arterial baroreceptor reflexes showed sympathetic nervous activity to be significantly elevated in alphaCGRP-null mice; elevated levels of urinary catecholamine metabolites and decreased HR variability in mutant mice were also consistent with that finding. These findings suggest that alphaCGRP contributes to the regulation of cardiovascular function through inhibitory modulation of sympathetic nervous activity.

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A 62-year-old man was admitted with increasing palpitations. Radiography of the chest demonstrated a calcified mass. Magnetic resonance imaging revealed compression of the right ventricle by a tumor. At the time of cardiac catheterization, the coronary arteries were found not to supply blood flow of the mass, and no dip-and-plateau pattern was seen in the right ventricular pressure measurements. At the time of surgery, the mass was found to be a focal calcified thickening of the pericardium containing only pus. The thickening resembled an oval pericardial tumor. Microbiologic examination of the pus revealed Propionibacterium acnes.

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Activated phagocytes are involved in the pathogenesis of Crohn's disease (CD). To clarify the activation of polymorphonuclear leukocytes (PMN) from CD patients in relationship with the clinical status, we investigated not only the expression of Fc receptor for IgG (huFc gamma R) but also the ability of the PMN to produce free oxygen radicals on stimulation of these receptors by using chemiluminescent techniques. The PMN obtained from the patients with active disease showed an enhanced chemiluminescence (CL) in response to huFc gamma RI stimulation, and an increased expression of huFc gamma RI. Moreover, PMN with huFc gamma RI were recognized in the colonic inflammatory lesions. After a successful treatment, however, we could hardly detect both the CL production and the expression of huFc gamma RI. Thus, it is suggested that the measurement of CL production through huFc gamma RI and the evaluation of the expression of huFc gamma RI are useful to evaluate the clinical status of the CD patients in a more accurate manner. The involvement of huFc gamma RI positive PMN in tissue destruction has been discussed.

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Ten patients with active Crohn's disease who have been managed with parenteral-nutrition therapy were administered a lipid emulsion either with [containing 0.6 g eicosapentaenoic acid (EPA)] or without fish oil for 2 wk. We isolated polymorphonuclear leukocytes (PMNLs) from the patients before and after this treatment and measured the amounts of leukotriene B4 (LTB4) and leukotriene B5 (LTB5) generated by activated PMNLs by reversed-phase HPLC. The LTB5 generation in active Crohn's disease before this treatment was significantly lower than in healthy control subjects. The amount of LTB5 and the LTB5-LTB4 ratio increased significantly after fish-oil supplementation. The difference with LTB4 was not statistically significant. We have shown that daily intravenous administration of 0.6 g EPA influenced the generation of leukotrienes in active Crohn's disease even after short-term treatment. Further investigations are necessary to clarify the correlation between EPA and clinical improvement in Crohn's disease.

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The herbal medicine "Sho-saiko-to (Xiao-Chai-Hu-Tang)" has been used in China for about 3000 years for the treatment of pyretic diseases. This medicine is now available as one of the prescribing drugs approved by the Ministry of Health and Welfare of Japan, and has also been widely used for patients with chronic viral liver disease as one of biological response modifiers in the field of Japan's Western Medicine. However, its mode of action has not been fully described. In the present in vitro study, we added "Sho-saiko-to" (TJ-9, Tsumura, Tokyo) to the culture of peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers, and observed a dose-dependent increase in the production of granulocyte colony-stimulating factor (G-CSF). The same experiment was conducted using other herbal medicines "Dai-saiko-to" (TJ-8) and "Saiko-keishi-to" (TJ-10) which showed similar effects, or "Sho-seiryu-to" (TJ-19) which consists of very different compounds and shows different efficacy. The increases of G-CSF production were similar when "Sho-saiko-to" (TJ-9) or one of the 2 reference drugs (TJ-8 and 10) was added, whereas the increase when the control drug "Sho-seiryu-to" (TJ-19) was added, was quite small. This result shows that G-CSF induction is not a common effect of herbal medicines, but a specific effect of TJ-8, 9, and 10. Among these 3 drugs the increase produced by "Sho-saiko-to" was the largest. Based on this result, we conclude that administration of "Sho-saiko-to" may be useful not only for the treatment of chronic liver disease, but also for malignant diseases and acute infectious diseases where G-CSF is efficacious.

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