Synthesis, isomerization, and antimicrobial evaluation of some pyrazolopyranotriazolopyrimidine derivatives

6-Amino-5-imino-pyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidine derivative 4 and pyrazolo-[4',3':5,6]pyrano[2,3-d]pyrimidin-5-ylhydrazine derivative 5 were prepared starting from 6-amino-3-methyl-4-(p-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile 1. The synthesis and structure characterization of 9,11-dihydropyrazolo[4',3':5,6]pyrano[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine derivatives 7 and 9 and their isomerization to 9,11-dihydropyrazolo[4',3':5,6]pyrano[3,2-e] [1,2,4]triazolo[1,5-c]pyrimidine derivatives 6 and 8, respectively, under different suitable reaction conditions are reported. Moreover, the synthesis of 9,11-dihydropyrazolo[4',3':5,6]pyrano[3,2-e] tetrazolo[1,5-c]pyrimidine derivative 14 and N(9)-acyclic nucleoside 15 are described. Some of the prepared products showed potent antimicrobial activity.     

Inflow reduction by distalization of anastomosis treats efficiently high-inflow high-cardiac output vascular access for hemodialysis

The arteriovenous fistula used for vascular access for hemodialysis may contribute to development of congestive heart failure. Theses patients can present with frequent episodes of congestive hear failure. Traditional management of high-inflow, a high-cardiac-output fistula generally involves either closure or banding. Although high-output state can be controlled, the lifeline of the patient is lost. We describe a series of 17 hemodialysis patients (10 men and 7 women) in whom a novel inflow reduction method was employed. All patients had symptoms of heart failure (15 brachiocephalic fistulas and two brachioaxillary bypass grafts) and a fistula inflow rate above 1600 ml/min. The inflow reduction procedure included ligation of the brachial anastomosis and reconstruction of the fistula by using an expanded polytetrafluoroethylene (Gore-Tex Intering) vascular graft in a bypass from the radial artery. The mean (+/- SD) time between fistula creation and the inflow reduction procedure was 30 +/- 17 months. The mean access inflow rate decreased significantly after the inflow reduction procedure, from 3135 +/- 692 to 1025 +/- 551 ml/min (p =0.0001). The mean cardiac output rate decreased from 8 +/- 3.1 to 5.6 +/- 1.7 l/min (p = 0.001) with resolution of symptoms. During the follow-up period thrombosis or stenosis developed in seven patients, three of whom underwent surgical revision. Thirteen of the seventeen accesses (77%) subjected to the inflow reduction procedure remained patent. Access loss was due to failed fistuloplasty or thrombosis. To our knowledge, this is the first report demonstrating that inflow reduction obtained by distalization of the anastomosis of the access fistula is feasible and safe for managing high-inflow, high-cardiac-output fistulas. Longer and larger studies of the inflow reduction procedure and its benefits are needed.     

Synthesis and investigation of anti-inflammatory activity and gastric ulcerogenicity of novel nitric oxide-donating pyrazoline derivatives

A group of 3,5-diaryl-2-pyrazoline derivatives were prepared via the reaction of various chalcones with hydrazine hydrate in ethanol. A group of NO-donating-2-pyrazoline derivatives were synthesized by carrying a nitrate ester group or an oxime group onto the prepared pyrazoline derivatives through different spacers. The prepared compounds were evaluated for their anti-inflammatory activity using carrageenan-induced rat paw edema and compared to a well-known NSAID, indomethacin as a reference drug. The ability of the prepared compounds to induce gastric toxicity was also evaluated. Most of the prepared compounds showed significant anti-inflammatory activity at the injected dose (100mg/kg) but they were safer than indomethacin in regard to gastric toxicity. The incorporation of the NO-donating group into the parent pyrazoline derivatives caused a non-significant reduction in the anti-inflammatory activity while a marked decrease in gastric ulcerations induced by their parent pyrazolines was observed.     

Using arteriovenous fistulae as a dual access for hemodialysis and total parenteral nutrition administration is feasible with a good outcome: a case series

End stage renal failure patients requiring long term total parenteral nutrition (TPN) often have multiple central line placements due to line infection or occlusion. Sometimes this can cause central venous stenosis or even occlusion. We present three cases in this consecutive series, in which we have successfully used arteriovenous fistulae for both hemodialysis and long term TPN administration as an alternative route without any complications. We therefore think that native AVF and grafts can be used as dual access for hemodialysis and TPN administration provided careful case selection, counselling and follow-up.