Abstract-We evaluated the development of arterial hypertension, cardiac function, and collagen deposition, as well as the level of components of the renin-angiotensin system in the heart of transgenic rats that overexpress an angiotensin (Ang)-(1-7)-producing fusion protein, TGR(A1-7)3292 (TG), which induces a lifetime increase in circulating levels of this peptide. After 30 days of the induction of the deoxycorticosterone acetate (DOCA)-salt hypertension model, DOCA-TG rats were hypertensive but presented a lower systolic arterial pressure in comparison with DOCA-SpragueDawley (SD) rats. In contrast to DOCA-SD rats that presented left ventricle (LV) hypertrophy and diastolic dysfunction, DOCA-TG rats did not develop cardiac hypertrophy or changes in ventricular function. In addition, DOCA-TG rats showed attenuation in mRNA expression for collagen type I and III compared with the increased levels of DOCA-SD rats. Ang II plasma and LV levels were reduced in SD and TG hypertensive rats in comparison with normotensive animals. DOCA-TG rats presented a reduction in plasma Ang-(1-7) levels; however, there was a great increase in Ang-(1-7) (Ϸ3-fold) accompanied by a decrease in mRNA expression of both angiotensin-converting enzyme and angiotensin-converting enzyme 2 in the LV. The mRNA expression of Mas and Ang II type 1 receptors in the LV was not significantly changed in DOCA-SD or DOCA-TG rats. This study showed that TG rats with increased circulating levels of Ang-(1-7) are protected against cardiac dysfunction and fibrosis and also present an attenuated increase in blood pressure after DOCA-salt hypertension. In addition, DOCA-TG rats showed an important local increase in Ang-(1-7) levels in the LV, which might have contributed to the attenuation of cardiac dysfunction and prefibrotic lesions. (Hypertension. 2010;55:889-896.)

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The techniques used for diagnosis of canine visceral leishmaniasis (CVL) in Brazil ELISA and IFAT have been extensively questioned because of the accuracy of these tests. A recent change in the diagnosis protocol excluded IFAT and included the Dual-Path Platform (DPP). We evaluated the prevalence and incidence rates of Leishmania spp. before and after the change in the protocol. In addition, based on our results, we propose a new alternative that is less expensive for the screening and confirmation of CVL. Plasma samples were obtained from a serobank from dogs evaluated in a cross-sectional study (1,226 dogs) and in a cohort study of susceptible animals (n = 447), followed for 26 months. Serology testing was performed using ELISA, IFAT, and DPP. The incidence and prevalence of CVL were determined by using the protocol of the Visceral Leishmaniasis Control and Surveillance Program until 2012 (ELISA and IFAT using filter paper) and the protocol used after 2012 (DPP and ELISA using plasma). The prevalence was 6.2% and the incidence was 2.8 per 1,000 dog-months for the protocol used until 2012. For the new diagnosis protocol for CVL resulted in an incidence of 5.4 per 1,000 dog-months and a prevalence of 8.1%. Our results showed that the prevalence and incidence of infection were far greater than suggested by the previously used protocol and that the magnitude of infection in endemic areas has been underestimated. As tests are performed sequentially and euthanasia of dogs is carried out when the serological results are positive in both tests, the sequence does not affect the number of animals to be eliminated by the Control Program. Then we suggest to municipalities with a large demand of exams to use ELISA for screening and DPP for confirmation, since this allows easier performance and reduced cost.

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In this study we investigated the effects of genetic deletion of the Angiotensin-(1-7) receptor Mas or the Angiotensin II receptor AT(2) on the expression of specific extracellular matrix (ECM) proteins in atria, right ventricles and atrioventricular (AV) valves of neonatal and adult mice. Quantification of collagen types I, III and VI and fibronectin was performed using immunofluorescence-labeling and confocal microscopy. Picrosirius red staining was used for the histological assessment of the overall collagen distribution pattern. ECM proteins, metalloproteinases (MMP), ERK1/2 and p38 levels were quantified by western blot analysis. Gelatin zymography was used to evaluate the activity of MMP-2 and MMP-9. We observed that the relative levels of collagen types I and III and fibronectin are significantly higher in both the right ventricle and AV valves of neonatal Mas(-/-) mouse hearts (e.g., collagen type I: 85.28±6.66 vs 43.50±4.41 arbitrary units in the right ventricles of Mas(+/+) mice). Conversely, the level of collagen type VI was lower in the right ventricle and AV valves of Mas(-/-) mice. Adult Mas(-/-) mouse hearts presented similar patterns as observed in neonates. No significant differences in ECM protein level were detected in atria. Likewise, no changes in ECM levels were observed in AT(2) knockout mouse hearts. Although deletion of Mas induced a significant reduction in the level of the active form of MMP-2 in neonate hearts and a reduction of both MMP-2 and MMP-9 in adult Mas(-/-) mice, no significant differences were observed in MMP enzymatic activities when compared to controls. The levels of the active, phosphorylated forms of ERK1/2 and p38 were higher in hearts of both neonatal and adult Mas(-/-) mice. These observations suggest that Mas is involved in the selective expression of specific ECM proteins within both the ventricular myocardium and AV valves. The changes in the ECM profile may alter the connective tissue framework and contribute to the decreased cardiac performance observed in Mas(-/-) mice.

Leishmaniases are diseases caused by several species. () can cause localized cutaneous leishmaniasis (LCL), which heals spontaneously, or mucosal leishmaniasis (ML), characterized by chronic and intense inflammation and scanty parasitism. Annexin A1 (AnxA1) is a protein involved in modulation and resolution of inflammation through multiple mechanisms. In the present study, the role of AnxA1 was investigated in-infected BALB/c mice. AnxA1 levels increased at the peak of tissue lesion and parasitism in infected mice. AnxA1 increased also after infection of BALB/c (wild-type [WT]) bone marrow derived macrophages. Despite a lower parasite intake, parasite burden in bone marrow-derived macrophages from AnxA1 mice was similar to WT and associated with an early increase of TNF-α and, later, of IL-10. AnxA1 mice controlled tissue parasitism similarly to WT animals, but they developed significantly larger lesions at later stages of infection, with a more pronounced inflammatory infiltrate and increased specific production of IFN-γ, IL-4, and IL-10. AnxA1 mice also presented higher phosphorylation levels of ERK-1/2 and p65/RelA (NF-κB) and inducible NO synthase expression, suggesting that AnxA1 may be involved in modulation of inflammation in this model of experimental leishmaniasis. Finally, assessment of AnxA1 levels in sera from patients with LCL or ML revealed that ML patients had higher levels of serum AnxA1 than did LCL patients or control subjects. Collectively, these data indicate that AnxA1 is actively expressed during infection. In the absence of AnxA1, mice are fully able to control parasite replication, but they present more intense inflammatory responses and delayed ability to resolve their lesion size.

Juvenile xanthogranuloma (JXG) is a dermatological condition of unknown etiology that rarely affects the oral mucosa. There are conflicting reports suggesting that it may represent a reactive virally-induced lesion associated with cytomegalovirus (CMV) infection. The present paper reports an additional case of oral JXG and discusses its possible association with CMV infection. The biotin-streptavidin system was used to detect early and late CMV antigens. Positive immunolabelling for both antigens was demonstrated in some histiocytes in the lesion. These findings suggest that JXG may be associated with CMV infection. (J. Oral Sci. 43, 21 -25 , 2001)