ATP steal between cation pumps: a mechanism linking Na+ influx to the onset of necrotic Ca2+ overload.

We set out to identify molecular mechanisms underlying the onset of necrotic Ca(2+) overload, triggered in two epithelial cell lines by oxidative stress or metabolic depletion. As reported earlier, the overload was inhibited by extracellular Ca(2+) chelation and the cation channel blocker gadolinium. However, the surface permeability to Ca(2+) was reduced by 60%, thus discarding a role for Ca(2+) channel/carrier activation. Instead, we registered a collapse of the plasma membrane Ca(2+) ATPase (PMCA). Remarkably, inhibition of the Na(+)/K(+) ATPase rescued the PMCA and reverted the Ca(2+) rise. Thermodynamic considerations suggest that the Ca(2+) overload develops when the Na(+)/K(+) ATPase, by virtue of the Na(+) overload, clamps the ATP phosphorylation potential below the minimum required by the PMCA. In addition to providing the mechanism for the onset of Ca(2+) overload, the crosstalk between cation pumps offers a novel explanation for the role of Na(+) in cell death.

Immunomodulation of LPS ability to induce the local Shwartzman reaction.

Immunologically, the septic shock is a natural model of immunomediated vascular pathology where the interaction between cytokines and the endothelium mediates the syndrome and lethality. Tumour necrosis factor (TNF), a non-species-specific cytokine, has outstanding pleiotropic activities as an important mediator of the septic shock syndrome. In rabbits, passive immunization with anti-lipopolysaccharide (LPS) polyclonal antibodies prior to the intravenous (i.v.) injection of LPS inhibits the haemorrhagic necrotic lesion characteristic of the local Shwartzman reaction (an excellent localized in vivo correlate of the septic shock). Paradoxically, tested in an ex vivo assay (short-term whole human blood culture, stimulated with LPS), these antibodies mediated an increase in TNF production by mononuclear phagocytes and, in the rabbit model, they induced an increase in body temperature, as compared with the pre-immune reagent. Although anchoring of immune complexes containing LPS to receptors (Fc or C4b-C3b) on circulating monocytes may facilitate the access of LPS to these cells, access to localized, LPS-sensitized macrophages may be impaired. Consequently inhibition of the local Shwartzman reaction and increased TNF production in the ex vivo system were observed. Concordantly, the higher temperature in the passively immunized animals may be a consequence of a higher, immune complex-induced, systemic TNF production. These experimental results suggest that the use of anti-LPS immunoglobulins, as a potential immunotherapy for septic shock syndrome in vertebrates, may lead to increased TNF production, with adverse effects such as the pyrogenic.

Purification and preliminary sequencing of Tc-45, an immunodominant Trypanosoma cruzi antigen: absence of homology with cruzipain, cruzain, and a 46-kilodalton protein.

In spite of being separated by more than 20 million years of evolution, the murine and human immune systems share extensive similarities. Thus, experimental results obtained with the murine model may have predictive value for human Chagas' disease. Challenge of the H-2 congenic mouse stains A.SW (H-2s) and A.CA (H-2f) with Trypanosoma cruzi yields different results. The A.CA animals die approximately 12 days postinfection, while A.SW mice survive indefinitely. A 45-kD protein (Tc45), an antigen differentially recognized by the A.SW strain, is present in cultured epimastigotes and blood trypomastigotes. We describe here its purification from epimastigotes. The presence of Tc45 was monitored and a single band was detected. Since the molecular weights of Tc45, cruzipain, cruzain, and a 46-kD parasite polypeptide are similar, it was important to determine if these molecules are related. A complete lack of homology was observed when the sequence of cruzain, cruzipain, and the 46-kD polypeptide were compared with the preliminary sequence of Tc45.

Tobacco, physical exercise and lipid profile.

A group of 572 young cadets from the General Military Academy in Zaragoza (AGEMZA) with a mean age of 19.9 years was studied in two different situations: on admission to the AGEMZA, when physical activity was very intensive (A) and after 8 months, by which time they had all received identical diets and physical activity was considerably reduced (B). On both occasions they were asked about their smoking habits and their personal and family histories. Their height and weight were recorded and a sample of venous blood was taken to determine the lipid, biochemical and haematological profiles. We found that more smokers had a family history of sudden death or acute myocardial infarction than the non-smokers. The smokers also showed a lower HDL cholesterol level (54.3 +/- 9.8 mg.dl-1 +/- SD) than the non-smokers (59.4 +/- 10.9) (P less than 0.0001) and a higher level of triglycerides (75.4 +/- 24.7 mg.dl-1) than the non-smokers (65.4 +/- 21.1 mg.dl-1). The smokers had a higher white cell count (8194 +/- 1981 vs 7332 +/- 1672 cells. 10mm-3) (P less than 0.001), a higher haemoglobin value (14.9 +/- 0.9 vs 14.6 +/- 0.9 g.dl-1) (P less than 0.004) and a higher haematocrit value (44.2 +/- 2.3 vs 43.6 +/- 2.7%) (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Primary angiosarcoma of the heart. A report of a new case and a review of the literature]. / Angiosarcoma primitivo de corazón (APC). Presentación de un nuevo caso y revisión de la literatura.

The case is presented of a primitive heart angiosarcoma (PHA) in a 53-year-old woman who developed repeated episodes of hemopericardium with cardiac tamponade. A literature review is performed. PHA is the most frequent primitive cardiac tumor. It is usually localized in the right striatum and is accompanied by effusion of pericardium and right heart failure. The diagnosis is usually made late and bidimensional echography is of great value. Treatment is surgical, if possible. Chemotherapy protocols are being used but with obscure prognosis.