The situation of infection in the elderly in Spain: a multidisciplinary opinion document.

Infection in the elderly is a huge issue whose treatment usually has partial and specific approaches. It is, moreover, one of the areas where intervention can have the most success in improving the quality of life of older patients. In an attempt to give the widest possible focus to this issue, the Health Sciences Foundation has convened experts from different areas to produce this position paper on Infection in the Elderly, so as to compare the opinions of expert doctors and nurses, pharmacists, journalists, representatives of elderly associations and concluding with the ethical aspects raised by the issue. The format is that of discussion of a series of pre-formulated questions that were discussed by all those present. We begin by discussing the concept of the elderly, the reasons for their predisposition to infection, the most frequent infections and their causes, and the workload and economic burden they place on society. We also considered whether we had the data to estimate the proportion of these infections that could be reduced by specific programmes, including vaccination programmes. In this context, the limited presence of this issue in the media, the position of scientific societies and patient associations on the issue and the ethical aspects raised by all this were discussed.

Hydrogen Sulfide Protects Renal Grafts Against Prolonged Cold Ischemia-Reperfusion Injury via Specific Mitochondrial Actions.

Ischemia-reperfusion injury is unavoidably caused by loss and subsequent restoration of blood flow during organ procurement, and prolonged ischemia-reperfusion injury IRI results in increased rates of delayed graft function and early graft loss. The endogenously produced gasotransmitter, hydrogen sulfide (H2 S), is a novel molecule that mitigates hypoxic tissue injury. The current study investigates the protective mitochondrial effects of H2 S during in vivo cold storage and subsequent renal transplantation (RTx) and in vitro cold hypoxic renal injury. Donor allografts from Brown Norway rats treated with University of Wisconsin (UW) solution + H2 S (150 µM NaSH) during prolonged (24-h) cold (4°C) storage exhibited significantly (p < 0.05) decreased acute necrotic/apoptotic injury and significantly (p < 0.05) improved function and recipient Lewis rat survival compared to UW solution alone. Treatment of rat kidney epithelial cells (NRK-52E) with the mitochondrial-targeted H2 S donor, AP39, during in vitro cold hypoxic injury improved the protective capacity of H2 S >1000-fold compared to similar levels of the nonspecific H2 S donor, GYY4137 and also improved syngraft function and survival following prolonged cold storage compared to UW solution. H2 S treatment mitigates cold IRI-associated renal injury via mitochondrial actions and could represent a novel therapeutic strategy to minimize the detrimental clinical outcomes of prolonged cold IRI during RTx.

Hydrogen sulfide donors alleviate itch secondary to the activation of type-2 protease activated receptors (PAR-2) in mice.

Hydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H2S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved. The intradermal injection of the PAR-2 peptide agonist SLIGRL-NH2 (8-80nmol) caused a dose-dependent scratching that was unaffected by intraperitoneal pre-treatment with the histamine H1 antagonist pyrilamine (30mg/kg). Co-injection of SLIGRL-NH2 (40nmol) with either the slow-release H2S donor GYY4137 (1 and 3nmol) or the spontaneous donor NaHS (1 and 0.3nmol) significantly reduced pruritus. Co-treatment with the KATP channel blocker glibenclamide (200nmol) or the nitric oxide (NO) donor sodium nitroprusside (10nmol) abolished the antipruritic effects of NaHS; however, the specific soluble guanylyl cyclase inhibitor ODQ (30µg) had no significant effects. The transient receptor potential ankyrin type 1 (TRPA1) antagonist HC-030031 (20µg) significantly reduced SLIGRL-NH2-induced pruritus; however pruritus induced by the TRPA1 agonist AITC (1000nmol) was unaffected by NaHS. Based on these data, we conclude that pruritus secondary to PAR-2 activation can be reduced by H2S, which acts through KATP channel opening and involves NO in a cyclic guanosine monophosphate (cGMP)-independent manner. Furthermore, TRPA1 receptors mediate the pruritus induced by activation of PAR-2, but H2S does not interfere with this pathway. These results provide additional support for the development of new therapeutical alternatives, mainly intended for treatment of pruritus in patients unresponsive to anti-histamines.

In search of adult renal stem cells.

The therapeutic potential of adult stem cells in the treatment of chronic degenerative diseases has becoming increasingly evident over the last few years. Significant attention is currently being paid to the development of novel treatments for acute and chronic kidney diseases too. To date, promising sources of stem cells for renal therapies include adult bone marrow stem cells and the kidney precursors present in the early embryo. Both cells have clearly demonstrated their ability to differentiate into the kidney's specialized structures. Adult renal stem cells have yet to be identified, but the papilla is where the stem cell niche is probably located. Now we need to isolate and characterize the fraction of papillary cells that constitute the putative renal stem cells. Our growing understanding of the cellular and molecular mechanisms behind kidney regeneration and repair processes - together with a knowledge of the embryonic origin of renal cells - should induce us, however, to bear in mind that in the kidney, as in other mesenchymal tissues, the need for a real stem cell compartment might be less important than the phenotypic flexibility of tubular cells. Thus, by displaying their plasticity during kidney maintenance and repair, terminally differentiated cells may well function as multipotent stem cells despite being at a later stage of maturation than adult stem cells. One of the major tasks of Regenerative Medicine will be to disclose the molecular mechanisms underlying renal tubular plasticity and to exploit its biological and therapeutic potential.

[Echopolycardiographic evaluation of left ventricular function after hemodialysis]. / Valutazione eco-policardiografica della funzionalità ventricolare sinistra dopo emodialisi.

The acute effects of haemodialysis on left ventricular (LV) function were studied by echocardiography and systolic time intervals in 19 patients maintained on long-term haemodialysis. Dialysis resulted in a significant reduction in body weight, an increase in heart rate and a small reduction in systolic blood pressure. A significant decrease was observed in LV diastolic and systolic dimensions, with an increase in the mean rate of circumferential shortening (mean VCF). The LV ejection time (LVET) decreased significantly, while changes in the pre-ejection period (PEP) were insignificant. The PEP/LVET ratio increased in all patients. Haemodialysis reduced the serum potassium levels; an increase was noted in the serum calcium concentrations, with a significant, although small, correction of blood pH. The major haemodynamic change induced by dialysis was a decrease in blood volume with a reduction in LV pre-load. These changes are suggested by the reduction in body weight and by the shortening in LV end-diastolic dimension and LVET. There was also a reduction in after-load, as expressed by the shortening in LV systolic diameter and by the decrease in systolic blood pressure. It should be emphasized that the study of LV function in patients on chronic dialysis is greatly influenced by the loading conditions. In such patients the assessment of LV function by echocardiography and systolic time intervals provides information regarding the haemodynamic changes induced by dialysis; however, no direct evidence can be derived about the functional state of the left ventricle.

Hydrolysis of phosphatidylethanolamine and phosphatidylglycerol by outer membrane phospholipase A from Acinetobacter sp. HO1-N.

An outer membrane phospholipase A active against phosphatidylglycerol and phosphatidylethanolamine was characterized from Acinetobacter sp. HO1-N.

Identification and synthesis of acyl-phosphatidylglycerol in Acinetobacter sp. HO1-N.

A minor phospholipid from Acinetobacter sp. HO1-N was identified as acyl-phosphatidylglycerol. Acyl-phosphatidylglycerol synthesis by outer-membrane preparations appeared to be a result of phospholipase A activity.

Characterization of lysocardiolipin from Acinetobacter sp. HO1-N.

Triacyl-lysocardiolipin (triacyl-LCL) and diacyl-LCL were isolated from Acinetobacter sp. HO1-N, and their structures were determined by chemical, physical, and enzymatic procedures. Deacylation of triacyl-LCL and diacyl-LCL yielded bis-glycerylphosphorylglycerol. Periodate oxidation of both lysolipids was negative. Diglyceride and 2-monoglyceride resulted from the acetic acid hydrolysis of triacyl-LCL, whereas 2-monoglyceride was the sole product obtained from diacyl-LCL. Cardiolipin (CL)-specific phospholipase D treatment of triacyl-LCL yielded lysophosphatidylglycerol and phosphatidic acid. Pancreatic lipase treatment of CL yielded triacyl-LCL and diacyl-LCL. 31P nuclear magnetic resonance spectrometry showed two resonance peaks separated by 40 HZ for CL, two overlapping peaks separated by 14 HZ for triacyl-LCL, and one peak for diacyl-LCL. The proportion of lysocardiolipin increased as a function of cell age, representing 2 to 3% of the total phospholipids in early- and mid-exponential growth, 5 to 7% in late-exponential growth, and 12% in the stationary growth phase.

Outer membrane phospholipase A from Acinetobacter sp. HO1-N.

A phospholipase A1 activity that hydrolyzed cardiolipin to triacyl- and diacyl-lysocardiolipin was localized in outer membrane preparations derived from Acinetobacter sp. HO1-N. The specific activity of the enzyme derived from hexadecane-grown cells was 2.5 to 3 times higher than that derived from NBYE-grown cells. An apparent Km of 2.22 mM was determined, although inhibition kinetics resulted at the higher cardiolipin substrate concentrations. Optimal reaction conditions established on metal requirements. Enzyme activity was obligately dependent on Triton X-100 (0.5%) and was inhibited by cationic and anionic detergents. Cardiolipin-specific phospholipase D converted triacyl-lysocardiolipin to lysophosphatidylglycerol and phosphatidic acid. The specific activity of this enzyme was approximately 100 times greater than that reported for other membrane preparations derived from microorganisms.