Acute on chronic limb ischemia: From surgical embolectomy and thrombolysis to endovascular options.

After the invention of the balloon catheter by Fogarty in 1963, surgical thromboembolectomy was considered the gold standard treatment for many years in patients with acute lower limb ischemia (ALLI). ALLI is a dramatic event, carrying a high risk of amputation and perioperative morbidity and mortality. The evolution of endovascular technologies has resulted in a variety of therapeutic options to establish arterial patency. In the 1970s, Dotter first introduced the idea of clot lysis in the treatment of ALLI, which was modified to catheter-directed thrombolysis, and now clot aspiration techniques. Currently, the majority of ALLI (about 70%) is arterial thrombosis, which generally occurs in the setting of preexisting vascular lesion. This condition is very common in patients with diabetes. Clinical presentation in case of thrombosis on atherosclerotic stenosis (so called "acute on chronic ischemia") may be less severe, but treatment is generally more challenging than ALLI due to embolism, considering the complexity in device trackability through the diseased vessels, potential vessel injury, incomplete revascularization, and need of correction of underlying vascular lesions. Although surgery is still a treatment option, especially for ALLI, endovascular interventions have assumed a prominent role in restoring limb perfusion. In this review, the treatment options for ALLI are detailed from surgical thromboembolectomy to thrombolysis and current endovascular techniques, including mechanical fragmentation, rheolytic thrombectomy, and aspiration thrombectomy. The evolution to endovascular therapies has resulted in improved clinical outcomes and lower rates of morbidity.

Physiology and pathology of nuclear phospholipase C ß1.

The existence and function of inositide signaling in the nucleus is well documented and we know that the existence of the inositide cycle inside the nucleus has a biological role. An autonomous lipid-dependent signaling system, independently regulated from its plasma membrane counterpart, acts in the nucleus and modulates cell cycle progression and differentiation.We and others focused on PLCß1, which is the most extensively investigated PLC isoform in the nuclear compartment. PLCß1 is a key player in the regulation of nuclear inositol lipid signaling, and, as discussed above, its function could also be involved in nuclear structure because it hydrolyses PtdIns(4,5)P2, a well accepted regulator of chromatin remodelling. The evidence, in a number of patients with myelodysplastic syndromes, that the mono-allelic deletion of PLCß1 is associated with an increased risk of developing acute myeloid leukemia paves the way for an entirely new field of investigation. Indeed the genetic defect evidenced, in addition to being a useful prognostic tool, also suggests that altered expression of this enzyme could have a role in the pathogenesis of this disease, by causing an imbalance between proliferation and apoptosis. The epigenetics of PLCß1 expression in MDS has been reviewed as well.

Ribavirin acts via multiple pathways in inhibition of leukemic cell proliferation.

UNLABELLED: The aim of this study was to elucidate the anticancer activity of Ribavirin, an antiviral drug and a known inhibitor of inositide-5'-monophosphate dehydrogenase. MATERIALS AND METHODS: Using human cancer cell lines, the potential of the drug to inhibit growth and induce the apoptotic and differentiation pathways was investigated by cytological methods. The effect exerted upon gene expression was studied in K562 cells by Q-PCR. RESULTS: Treatment with Ribavirin resulted in a significant growth inhibition (IC(50)=15 microM) via activating apoptosis and the differentiation pathway in K562 cells. It also modulated the expression of about 60 out of 85 genes having roles in cell proliferation, purine biosynthesis, translation initiation, oncogenic signaling and cell survival (p<0.05). CONCLUSION: Ribavirin is a potent anticancer agent, being a strong inducer of apoptosis and a moderate inducer of differentiation in K562 cells. These effects are mediated through the modulation of key molecular and metabolic pathways.

Down-regulation of increased signal transduction capacity in human cancer cells.

Signal transduction capacity in human cancer cells is constitutively up-regulated by the markedly increased steady-state activities of the three synthetic enzymes, PI kinase, PIP kinase and PLC, which catalyze the conversion of PI to the second messengers IP3 and DAG. This evidence is supported by the elevated concentration of IP3 in human colon, ovarian and breast carcinoma samples and rat hepatocellular carcinomas and sarcoma. The decrease in activities of the two specific phosphatases in the degradative pathway of signal transduction provides an amplified capacity for IP3 production. The elevated second messenger concentrations should lead to increased calcium release and protein kinase C activation. These biochemical alterations should confer selective biological advantages to cancer cells. The malignancy-linked rise in the activity of the signal transduction pathway can be down-regulated by drugs (tiazofurin, ribavirin, tamoxifen) or through inhibition of the kinases by flavonoids (quercetin, genistein) which lead to a reduction of IP3 concentration. As a result, carcinoma cells in culture stop proliferating and are destroyed. The stringent linkage of signal transduction with neoplasia provides novel targets for clinical chemotherapy.

Control of Escherichia coli O157:H7 with sodium metasilicate.

Three intervention strategies-trisodium phosphate, lactic acid, and sodium metasilicate--were examined for their in vitro antimicrobial activities in water at room temperature against a three-strain cocktail of Escherichia coli O157:H7 and a three-strain cocktail of "generic" E. coli. Both initial inhibition and recovery of injured cells were monitored. When 3.0% (wt/wt) lactic acid, pH 2.4, was inoculated with E. coli O157:H7 (approximately 6 log CFU/ml), viable microorganisms were recovered after a 20-min exposure to the acid. After 20 min in 1.0% (wt/wt) trisodium phosphate, pH 12.0, no viable E. coli O157:H7 microorganisms were detected. Exposure of E. coli O157:H7 to sodium metasilicate (5 to 10 s) at concentrations as low as 0.6%, pH 12.1, resulted in 100% inhibition with no recoverable E. coli O157:H7. No difference in inhibition profiles was detected between the E. coli O157:H7 and generic strains, suggesting that nonpathogenic strains may be used for in-plant sodium metasilicate studies.

Current role of the minimally invasive direct aortic surgery for 3-A repair (MIDAS-3A).

Open aneurysmectomy and aortic graft is still associated with a relatively high morbidity and mortality. To decrease this surgical stress, less invasive procedure, MIDAS-3A technique (Minimally Invasive Direct Aortic Surgery for AAA) was developed, utilizing a 5 cm abdominal incision and a video-laparoscopic assistance (gas-less) to reach the AAA retroperitoneally. From Nov. 1999 to Dec. 2002, 80 patients underwent surgery. This technique provides all the benefits of an open surgical approach, to be combined with the advantages derived from minimized tissue trauma. A comparison between MIDAS-3A and CL (Conventional Laparotomy) was performed, monitorizing-nasogastric drainage;--initial feeding;--pulmonary functions (Vital Capacity, and Forced Expiration Volume);--Intensive Care Unit recovery (long stay);--length of hospital stay;--operative time;--blood loss. The perioperative (30 days) mortality (2.5%), and the morbidity (7.5%) was equal in both groups. No conversion to conventional laparotomy occurred. MIDAS-3A has significantly reduced length of hospital stay (3.5 days), and pulmonary dysfunctions. This technique provides all the benefits of open surgical approach, to be combined with the advantages derived from minimized tissue trauma. MIDAS-3A reduced trauma and pain, which resulted in a shorter hospital stay, and so lower expense and better financial consequences.

Assay Procedures for Commercial Probiotic Cultures.

A number of commercially available cultures, marked for human consumption, were analyzed for viability using a resuspension medium consisting of KH2PO4, Na2HPO4, cysteine, Tween 80, agar, and an antifoam agent together with modifications of multiple-layer diffusion techniques. These methods were compared to the use of MRS plus cysteine, acidified MRS, and M17 culture media and found to be superior in the selection and enumeration of dried cultures of mixed genera.