Activation of the ER stress and calcium signaling in angiomyolipoma.

Renal angiomyolipomas (AMLs) are uncommon benign tumors that occur sporadically or as a part of tuberous sclerosis complex (TSC). Risk of life threatening hemorrhage is the main clinical concern. Although several evidences suggest that hyper-activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway is crucial for these tumors, modulation of other metabolic pathways might affect tumor growth and progression. Therefore, we aimed to further characterize angiomyolipoma by TSC1/TSC2 expression, hypoxic status, expression of endoplasmic reticulum (ER) stress markers and calcium transport from the ER through the inositol 1,4,5-trisphosphate (IP3) receptors. Despite our expectations, angiomyolipoma were not hypoxic, as determined by absent expression of the carbonic anhydrase IX, which is a reliable marker of hypoxia. This was in accord with very low expression of TSC1 (that is associated with HIF activation) and a high expression of TSC2. Angiomyolipoma specimens also showed a significant upregulation of an anti-apoptotic marker Bcl2 when compared to healthy kidney tissue supporting the induction of pro-survival signaling. Moreover, angiomyolipoma specimens showed the overexpression of the ER stress markers XBP1, CHOP and ATF4 as well as of the mediators of calcium metabolism, namely the type 1 and 2, but not the type 3 IP3 receptors. These data suggest that the ER stress response, survival and calcium metabolism-related pathways but not hypoxia is an important component of the angiomyolipoma pathogenesis.

Captopril partially decreases the effect of H(2)S on rat blood pressure and inhibits H(2)S-induced nitric oxide release from S-nitrosoglutathione.

We studied the effects of the H(2)S donor Na(2)S on the mean arterial blood pressure (MAP) and heart and breathing rates of anesthetized Wistar rats in the presence and absence of captopril. Bolus administration of Na(2)S (1-4 micromol/kg) into the right jugular vein transiently decreased heart and increased breathing rates; at 8-30 micromol/kg, Na(2)S had a biphasic effect, transiently decreasing and increasing MAP, while transiently decreasing heart rate and increasing and decreasing breathing rate. These results may indicate independent mechanisms by which H(2)S influences MAP and heart and breathing rates. The effect of Na(2)S in decreasing MAP was less pronounced in the presence of captopril (2 micromol/l), which may indicate that the renin-angiotensin system is partially involved in the Na(2)S effect. Captopril decreased H(2)S-induced NO release from S-nitrosoglutathione, which may be related to some biological activities of H(2)S. These results contribute to the understanding of the effects of H(2)S on the cardiovascular system.

Citius, altius, fortius in 2001.

Since the inclusion of the Croatian Medical Journal into MEDLINE (1998) and Current Contents/Clinical Medicine (1999), the number of manuscripts submitted to it for publication has been continually increasing. This fact required many changes in the Journal and its editorial policy. The editorial board has decided to increase the number of issues published per year from four to six. To improve the scientific quality of the journal, the Croatian Medical Journal Committee of Research Integrity has been established. The committee will actively deal with all aspects of research integrity related to submitted manuscripts. More attention will also be paid to statistical review of the manuscripts. Another innovation, which aims at medical student readership, is the launch of the Student CMJ. It will be published once a year as part of the Croatian Medical Journal. Also, a regular new column under the title Health Watch starts with this year. Hopefully, all these changes will contribute to the Journal's quality, increase its visibility, and attract a broader readership.