The curative effect of cannabinoid 2 receptor agonist on functional failure and disruptive inflammation caused by intestinal ischemia and reperfusion

Ischemia and reperfusion of intestinal tissue (intestinal I/R) induce disruption of ileal contractility and chain responses of inflammatory. The aim of this study was to reveal whether therapeutic value of cannabinoid 2 (CB2) receptor activity in the intestinal I/R, via to the exogenous administration of CB2 agonist (AM-1241). Intestinal I/R injury were performed through 30-min ischemia and 150-min reperfusion of mesenteric artery in Wistar rats. The pre-administered doses of 0.1, 1, and 5 mg/kg of CB2 agonist were studied to inhibit inflammation of intestinal I/R injury including ileum smooth muscle contractility, polymorphonuclear cell migration, oxidant/antioxidant defense system, and provocative cytokines. Pre-administration with CB2 receptor agonist ensured to consider improving the disrupted contractile responses in ileum smooth muscle along with decreased the formation of MDA that production of lipid peroxidation, reversed the depleted glutathione, inhibited the expression of TNF-α and of IL-1β in the intestinal I/R of rats. Taken together results of this research, the agonistic activity of CB2 receptor for healing of intestinal I/R injury is ensuring associated with anti-inflammatory mechanisms such as the inhibiting of migration of inflammatory polymorphonuclear cells that origin of acute and initial responses of inflammation, the inhibiting of production of provocative and pro-inflammatory cytokines like TNF-α and IL-1β, the rebalancing of oxidant/antioxidant redox system disrupted in injury of reperfusion period and the supporting of physiologic defensive systems in endothelial and inducible inflammatory cells.     

Impact of early tirofiban administration on myocardial salvage in patients with acute myocardial infarction undergoing infarct-related artery stenting

BACKGROUND/AIMS: The timing of GpIIb/IIIa inhibitor administration may be important in achieving early epicardial and myocardial reperfusion. We evaluated the effect of early tirofiban on myocardial salvage and cardiovascular outcome in patients with acute myocardial infarction (AMI) undergoing infarct-related artery stenting. METHODS: Patients (n = 66) with a first AMI presenting <6 h from onset of symptoms were randomized to either early administration of tirofiban in the emergency room (n = 32) or later administration in the catheterization laboratory (n = 34) (tirofiban bolus dose of 10 microg/kg, followed by 0.15 microg/kg for 24 h). The primary end-point was the degree of myocardial salvage, determined by means of serial scintigraphic studies with technetium-99m sestamibi. Thirty-day major adverse cardiac events were also assessed. RESULTS: There were no significant differences in patient characteristics or in their presentation. The mean door-to-balloon time was similar in both groups (43 +/- 12 and 53 +/- 9 min, p = 0.08). The early and late treatment groups received tirofiban 18 +/- 4 and 52 +/- 10 min after admission, respectively. Angiographic analysis revealed a higher initial frequency of TIMI grade 3 flow in the early group (31% vs. 12%, p = 0.04). Procedural success was achieved in all patients. Myocardial risk area were comparable between early and late treatment groups (35.6 +/- 12.2% vs. 39.3 +/- 14.0%, p = 0.6). Scintigraphic outcomes demonstrated a significant reduction in the final infarction size (11.8 +/- 5.2% vs. 22.4 +/- 6.2%, p = 0.01), and improvement in salvage index (0.68 +/- 0.22 vs. 0.44 +/- 0.18, p = 0.003) in favor of the early tirofiban group. The thirty-day composite end-point of death, recurrent MI or rehospitalization also favored the early group (6% early, 15% late, p = 0.06). CONCLUSION: Early tirofiban administration enhanced the degree of myocardial salvage and clinical outcome in patients with AMI undergoing infarct-related artery stenting.     

Chromosome changes in metastatic human melanoma

Cytogenetic studies were performed on human malignant melanoma cells from eight metastatic lesions. Five tumors displayed near-triploid and three near-diploid chromosome numbers. Chromosomes #1,#6,#7, followed by #2 and #9, were found to be most frequently involved in structural aberrations. Aberrations involving chromosome #1, with deletions or translocations of 1p, involving region 1p12-1p22 in seven of eight breakpoints of the p arm were observed. Seven of nine breakpoints of 6q were located at region 6q15-6q21. Most of the breakpoints on chromosome #7 occurred near the centromeric region. All tumors had additional chromosome material involving 1q, chromosome #7 (7q in two tumors), and in five tumors an increased dose of chromosome #6 (6p in one tumor). The nonrandom breakpoints of these and other chromosomes involved diverse bands, including loci of oncogenes and fragile sites. The observation of nonrandom chromosomal changes in advanced malignant melanoma suggests that genes important in the progression of melanoma are located on chromosomes #1,#6, and #7.     

Letter to the editor

A response to Dango S, Lin R, Hennings E, Passlick B. Initial experience with a synthetic sealant PleuraSeal ™ after pulmonary resections: a prospective study with retrospective case matched controls. Journal of Cardiothoracic Surgery 2010, 5 :50.     

Mixed steroidal 1,2,4,5-tetraoxanes: antimalarial and antimycobacterial activity

Mixed 1,2,4,5-tetraoxanes possessing simple spirocycloalkane and spirocholic acid-derived substituents were prepared and shown to have significantly higher in vitro antimalarial activity than bis-substituted tetraoxanes. Out of 41 synthesized tetraoxanes, 12 were in vitro more potent against Plasmodium falciparum chloroquine-resistant W2 clone than artemisinin, and the most potent one was 2.4 times as active as arteether. In addition, 9 compounds exhibit higher activity than chloroquine against P. falciparum chloroquine-susceptible D6 clone. Cytotoxicity was assessed for most active compounds against the Vero cell line, showing a cytotoxicity/antimalarial potency ratio of 1/(1400-9500). For the first time, tetraoxanes were screened against Mycobacterium tuberculosis with MICs as low as 4.73 microM against H37Rv strain. Mixed tetraoxanes were synthesized in a simple procedure from cholic acid methyl esters by direct coupling of steroidal gem-dihydroperoxide to simple ketones and further transformed into corresponding acids and amides.     

Chemical necrotizing fasciitis due to household insecticide injection: is immediate radical surgical debridement necessary?

We describe two cases of chemical necrotizing fasciitis in the upper extremities, anterior chest wall and epigastric region of the abdominal wall caused by household insecticide injection. We suggest that surgical debridement can be successfully performed in the subacute period under close observation in hemodynamically stable patients.     

Treatment of iatrogenic internal carotid artery laceration and carotid cavernous fistula with endovascular stent-graft placement

The risk of fatal injury of the internal carotid artery (ICA) and surrounding anatomy during transsphenoidal surgery for pituitary adenoma is the most severe potential complication associated with this particular approach. We present a case in which iatrogenic injury to a patient's ICA and resultant carotid cavernous fistula and massive hemorrhage was successfully managed with the emergency placement of an endovascular stent-graft. Both findings in the relevant literature and practical considerations concerning both stent-grafts and other more commonly used options for the treatment of iatrogenic ICA injury are discussed.