Surgical strategy of abdominal aortic aneurysm with preoperative renal failure

Objectives:To determine the effect of preoperative renal failure on the outcome of patients suffering from infrarenal abdominal aortic aneurysm (AAA).Method:During the period from January 1979 to August 1995, 364 patients with AAA were admitted to our hospital and 323 underwent elective reapir. The patients were retrospectively analysed in three groups. Group I was composed of 273 patients with a normal renal function who underwent an aneurysm repair. Group II was composed of 50 patients who demonstrated a preoperative renal dysfunction (creatinine above 2.0 mg/dl or creatinine clearance below 40 ml/min) and underwent an operation, including three patients maintained on chronic haemodialysis. Group III was composed of 18 patients with a renal dysfunction who did not undergo repair, including one patient maintained on chronic haemodialysis.Results:The operative mortality rate of groups I and II were 0.4% and 2.0%, respectively, although no significant difference was observed. The incidence of postoperative cardiac and pulmonary complications were also comparable in two groups. No patients required acute haemodialysis. The 5-year survival rate of group II (44%) was significantly higher than that of group III (20%), and seven of the 18 patients (39%) in group III ultimately died of a rupture of the AAA.Conclusions:Patients with chronic renal failure can undergo an abdominal aortic aneurysm repair based on the same indications as those without renal failure

The Outcome of the Axillofemoral Bypass: A Retrospective Analysis of 45 Patients

Purpose This study was designed to retrospectively analyze outcomes of axillofemoral bypass (AxFB) operations performed in patients with severe comorbidities. Methods All patients (n = 45) who received an AxFB between 1990 and 2005 for aortoiliac occlusive disease (AIOD, n = 35) or infectious aortic disease (IAD, n = 10) were included. Information on patency of the bypass and mortality was retrieved from patient records. A Kaplan-Meier survival analysis was performed to illustrate survival rates, limb salvage, and primary and secondary patency. Results Included patients had several comorbidities and a high operative risk. In this group, a 30-day mortality rate of 20% was found: 17% for the AIOD group, and 30% for the IAD group. During 5-year follow-up 20 patients died, of which 15 during the first year after operation. Survival rates were at 64 and 41% at 1 and 5 years and limb salvage rates were 84% for both these years. Primary patency rates at 1 and 5 years were 72 and 58%, respectively, and secondary patency rates were 86% at both time points. Conclusions High mortality rates were found in AIOD or IAD patients who received an AxFB. However, for high-risk patients with an already reduced life expectancy, the AxFB remains an alternative with acceptable patency rate

The RNA Binding Protein SAM68 Transiently Localizes in the Chromatoid Body of Male Germ Cells and Influences Expression of Select MicroRNAs

The chromatoid body (CB) is a unique structure of male germ cells composed of thin filaments that condense into a perinuclear organelle after meiosis. Due to the presence of proteins involved in different steps of RNA metabolism and of different classes of RNAs, including microRNAs (miRNAs), the CB has been recently suggested to function as an RNA processing centre. Herein, we show that the RNA binding protein SAM68 transiently localizes in the CB, in concomitance with the meiotic divisions of mouse spermatocytes. Precise staging of the seminiferous tubules and co-localization studies with MVH and MILI, two well recognized CB markers, documented that SAM68 transiently associates with the CB in secondary spermatocytes and early round spermatids. Furthermore, although SAM68 co-immunoprecipitated with MVH in secondary spermatocytes, its ablation did not affect the proper localization of MVH in the CB. On the other hand, ablation of the CB constitutive component MIWI did not impair association of SAM68 with the CB. Isolation of CBs from Sam68 wild type and knockout mouse testes and comparison of their protein content by mass spectrometry indicated that Sam68 ablation did not cause overall alterations in the CB proteome. Lastly, we found that SAM68 interacts with DROSHA and DICER in secondary spermatocytes and early round spermatids and that a subset of miRNAs were altered in Sam68−/−germ cells. These results suggest a novel role for SAM68 in the miRNA pathway during spermatogenesis

Novel insights into the mechanisms mediating the local antihypertrophic effects of cardiac atrial natriuretic peptide: role of cGMP-dependent protein kinase and RGS2

Cardiac atrial natriuretic peptide (ANP) locally counteracts cardiac hypertrophy via the guanylyl cyclase-A (GC-A) receptor and cGMP production, but the downstream signalling pathways are unknown. Here, we examined the influence of ANP on β-adrenergic versus Angiotensin II (Ang II)-dependent (Gs vs. Gαq mediated) modulation of Ca2+i-handling in cardiomyocytes and of hypertrophy in intact hearts. L-type Ca2+ currents and Ca2+i transients in adult isolated murine ventricular myocytes were studied by voltage-clamp recordings and fluorescence microscopy. ANP suppressed Ang II-stimulated Ca2+ currents and transients, but had no effect on isoproterenol stimulation. Ang II suppression by ANP was abolished in cardiomyocytes of mice deficient in GC-A, in cyclic GMP-dependent protein kinase I (PKG I) or in the regulator of G protein signalling (RGS) 2, a target of PKG I. Cardiac hypertrophy in response to exogenous Ang II was significantly exacerbated in mice with conditional, cardiomyocyte-restricted GC-A deletion (CM GC-A KO). This was concomitant to increased activation of the Ca2+/calmodulin-dependent prohypertrophic signal transducer CaMKII. In contrast, β-adrenoreceptor-induced hypertrophy was not enhanced in CM GC-A KO mice. Lastly, while the stimulatory effects of Ang II on Ca2+-handling were absent in myocytes of mice deficient in TRPC3/TRPC6, the effects of isoproterenol were unchanged. Our data demonstrate a direct myocardial role for ANP/GC-A/cGMP to antagonize the Ca2+i-dependent hypertrophic growth response to Ang II, but not to β-adrenergic stimulation. The selectivity of this interaction is determined by PKG I and RGS2-dependent modulation of Ang II/AT1 signalling. Furthermore, they strengthen published observations in neonatal cardiomyocytes showing that TRPC3/TRPC6 channels are essential for Ang II, but not for β-adrenergic Ca2+i-stimulation in adult myocytes

Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons.

An increasing number of studies show that the activation of the innate immune system and inflammatory mechanisms play an important role in the pathogenesis of numerous diseases. The innate immune system is present in almost all multicellular organisms and its activation occurs in response to pathogens or tissue injury via pattern-recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Intracellular pathways, linking immune and inflammatory response to ion channel expression and function, have been recently identified. Among ion channels, the transient receptor potential (TRP) channels are a major family of non-selective cation-permeable channels that function as polymodal cellular sensors involved in many physiological and pathological processes.In this review, we summarize current knowledge of interactions between immune cells and PRRs and ion channels of TRP families with PAMPs and DAMPs to provide new insights into the pathogenesis of inflammatory diseases. TRP channels have been found to interfere with innate immunity via both nuclear factor-kB and procaspase-1 activation to generate the mature caspase-1 that cleaves pro-interleukin-1ß cytokine into the mature interleukin-1ß.Sensory neurons are also adapted to recognize dangers by virtue of their sensitivity to intense mechanical, thermal and irritant chemical stimuli. As immune cells, they possess many of the same molecular recognition pathways for danger. Thus, they express PRRs including Toll-like receptors 3, 4, 7, and 9, and stimulation by Toll-like receptor ligands leads to induction of inward currents and sensitization in TRPs. In addition, the expression of inflammasomes in neurons and the involvement of TRPs in central nervous system diseases strongly support a role of TRPs in inflammasome-mediated neurodegenerative pathologies. This field is still at its beginning and further studies may be required.Overall, these studies highlight the therapeutic potential of targeting the inflammasomes in proinflammatory, autoinflammatory and metabolic disorders associated with undesirable activation of the inflammasome by using specific TRP antagonists, anti-human TRP monoclonal antibody or different molecules able to abrogate the TRP channel-mediated inflammatory signals