Raising plasma phosphorus levels by phosphorus-enriched, bicarbonate-containing dialysate in hemodialysis patients

In 6 hemodialysis patients, enriching the "base concentrate" of a bicarbonate-containing dialysate-generating system with phosphorus succeeded in raising plasma phosphorus levels.     

Validation of serotonin (5-hydroxtryptamine) as an in vitro substrate probe for human UDP-glucuronosyltransferase (UGT) 1A6.

Investigation of human UDP-glucuronosyltransferase (UGT) isoforms has been limited by a lack of specific substrate probes. In this study serotonin was evaluated for use as a probe substrate for human UGT1A6 using recombinant human UGTs and tissue microsomes. Of the 10 commercially available recombinant UGT isoforms, only UGT1A6 catalyzed serotonin glucuronidation. Serotonin-UGT activity at 40 mM serotonin concentration varied more than 40-fold among human livers (n = 54), ranging from 0.77 to 32.9 nmol/min/mg of protein with a median activity of 7.1 nmol/min/mg of protein. Serotonin-UGT activity kinetics of representative human liver microsomes (n = 7) and pooled human kidney, intestinal and lung microsomes and recombinant human UGT1A6 typically followed one enzyme Michaelis-Menten kinetics. Serotonin glucuronidation activity in these human liver microsomes had widely varying V(max) values ranging from 0.62 to 51.3 nmol/min/mg of protein but very similar apparent K(m) values ranging from 5.2 to 8.8 mM. Pooled human kidney, intestine, and lung microsomes had V(max) values (mean +/- standard error of the estimates) of 8.8 +/- 0.4, 0.22 +/- 0.00, and 0.03 +/- 0.00 nmol/min/mg of protein (respectively) and apparent K(m) values of 6.5 +/- 0.9, 12.4 +/- 2.0, and 4.9 +/- 3.3 mM (respectively). In comparison, recombinant UGT1A6 had a V(max) of 4.5 +/- 0.1 nmol/min/mg of protein and an apparent K(m) of 5.0 +/- 0.4 mM. A highly significant correlation was found between immunoreactive UGT1A6 protein content and serotonin-UGT activity measured at 4 mM serotonin concentration in human liver microsomes (R(s) = 0.769; P < 0.001) (n = 52). In conclusion, these results indicate that serotonin is a highly selective in vitro probe substrate for human UGT1A6.     

Recent advances in the pharmacotherapy of chronic anal fissure: an update

Surgical sphincterotomy reduces anal tone and sphincter spasm and promotes ulcer healing. Because the surgery is associated with the side effect of faecal incontinence, pharmacological agents to treat chronic anal fissure have been explored recently. Glyceryl trinitrate (GTN) ointment (0.2%) has an efficacy of up to 68% in healing chronic anal fissure, but it is associated with headache as the major and most common side effect. Though botulinum toxin injected into the anal sphincter healed over 80% of chronic anal fissures, it is more invasive and expensive than GTN therapy. Diltiazem ointment achieved healing of chronic anal fissure comparable to 0.2% GTN ointment but was associated with fewer side effects. Other drugs that have been tried are lidocaine, the alpha-adrenergic antagonist indoramin, and the potassium channel opener minoxidil.     

Intentional internal iliac artery occlusion to facilitate endovascular repair of aortoiliac aneurysms

PURPOSE: The safety of intentional occlusion of patent internal iliac arteries (IIAs) to facilitate the endovascular repair of aortoiliac artery aneurysms (abdominal aortic aneurysms [AAAs] and iliac aneurysms [IAs]) was evaluated. METHODS: We analyzed the techniques and clinical sequelae of selective occlusion of one or both IIAs in 103 patients and correlated these findings with the results of preoperative angiograms to identify vascular anatomy that may predict postoperative pelvic ischemia. To quantify the clinical presentation of pelvic ischemia, we developed these criteria: class 0, no symptoms; class I, nonlimiting claudication with exercise; class II, new onset impotence, with or without moderate to severe buttock pain, leading to physical limitation with exercise; class III, buttock rest pain, colonic ischemia, or both. IIA occlusion was achieved in 100% of the patients by means of either catheter-directed embolization or orificial coverage with a stent-graft. No patient in this study had angiographic evidence of significant visceral occlusive disease before the procedure. Sixty-four patients had isolated AAAs, 23 patients had AAAs and IAs, and 16 patients had isolated IAs. Ninety-two patients had one IIA selectively occluded, and 11 patients had both IIAs selectively occluded. RESULTS: After IIA occlusion, 12 patients were categorized in class I, 9 patients were categorized in class II, and 1 patient was categorized in class III, for a total of 22 patients (21%) with pelvic ischemia. Sixteen (17%) of 92 patients had unilateral IIA occlusions, and six (17%) of 11 patients had bilateral IIA occlusions. Five patients in class I improved and had no symptoms within 1 year, and one patient in class II was downgraded to class I because of improved symptoms. Two unique preoperative angiographic findings were identified in the remaining 16 patients (16%) with chronic pelvic claudication: (1) stenosis of the remaining IIA origin (> 70%) with nonopacification of more than three of the six IIA branches (63%); and (2) small caliber, diseased or absent medial and lateral femoral circumflex arteries ipsilateral to the side of the IIA occlusion (25%). One patient with class III ischemia died of cardiovascular collapse associated with colon infarction caused by either acute ischemia or particulate embolization. CONCLUSION: The incidence of pelvic ischemia after IIA occlusion is 20% immediately after endovascular aortoiliac aneurysm repair. A total of 25% of patients had no symptoms within 1 year. Two preoperative radiologic findings may help identify patients who are at risk for pelvic ischemia: stenosis of the patent IIA and disease deep femoral ascending branches ipsilateral to the occluded IIA. The risk of colon ischemia appears to be small after selective IIA occlusion to facilitate endovascular AAA repair.     

Ring-opening cyclization of activated spiro-aziridine oxindoles with heteroarenes: a facile synthetic approach to spiro-oxindole-fused pyrroloindolines

Herein, we report a facile tandem approach for the synthesis of both spiro-oxindole-fused pyrroloindolines and benzofurano-pyrrolidines via a Lewis acid-catalyzed domino ring-opening with concomitant ring annulation using activated spiro-aziridines and heteroarenes. This method offers a new class of novel spiro-fused polycyclic pyrrolidines in a one-pot and sustainable manner with good yields and high diastereoselectivity. In addition, the structure of 3d was confirmed by single X-ray crystallography analysis.

Herein, we report a facile tandem approach for the synthesis of both spiro-oxindole-fused pyrroloindolines and benzofurano-pyrrolidines via a Lewis acid-catalyzed domino ring-opening annulation using activated spiro-aziridines and heteroarenes.     

β-Asarone Exhibits Antifungal Activity by Inhibiting Ergosterol Biosynthesis in Aspergillus niger ATCC 16888

Fungi play an important role in the degradation of leather goods. Economics often influence the choice of fungicide, thus, search for highly effective and low cost fungicides is immensely important. The authors have screened antifungal activity of ten Indian traditional medicinal plants viz Acalypha fruticosa, Acalypha indica, Aegle marmelos, Adathoda vasika, Calotropis gigantea, Erythrina indica, Morinda citrifolia, Nerium oleander, Pithecellobium dulce, and Acorus calamus based upon their traditional knowledge and usage. Various solvent extracts and essential oils were screened for antifungal activity against Aspergillus niger. The antifungal potency was compared to untreated control and standard antifungal drugs itraconazole and voriconazole. The bioactive principle from highly active fragment was isolated and chemically characterized. The mode of action was determined by a range of studies that include the lesion of plasma membrane, ergosterol content in the plasma membrane, acidification of external medium, and mitochondrial dehydrogenase activity in A. niger ATCC 16888. Among the ten plants studied, A. calamus exhibited greater antifungal potency in comparison to untreated control and standard drugs itraconazole and voriconazole. The minimum inhibitory concentration of both methanolic extract and essential oil of A. calamus against A. niger ATCC 16888 is around 5 µg/ml. The authors identified β-Asarone as the bioactive principle of A. calamus using spectral studies viz ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy and gas chromatography coupled mass spectroscopy. The results indicate that β-Asarone interfere and reduces the ergosterol content in the plasma membrane of A. niger ATCC 16888 thus exert their antifungal activity.

     

Validation of the Maryland Aggregate Pathology Index (MAPI), a pre‐implantation scoring system that predicts graft outcome

Predicting graft outcome after renal transplantation based on donor histological features has remained elusive and is subject to institutional variability. We have shown in a retrospective study that the Maryland Aggregate Pathology Index score reliably predicts graft outcome. We sought to validate the scoring system in our center and a second transplant center. We analyzed 140 deceased donor kidneys pre‐implantation biopsies from center 1 and 65 from center 2. The patients had a mean follow‐up of 695 ± 424 and 656 ± 305 d respectively. Although MAPI scores were similar, there were significant differences in donor and recipient parameters between both centers. Despite this, MAPI was predictive of graft outcome for both centers by Cox univariate, multivariate and time dependent ROC analysis. For center 1 and 2, three yr graft survival within each MAPI group was statistically equivalent. The three‐yr graft survival at center 1 for low, intermediate, and high MAPI groups were 84.3%, 56.5%, and 50.0%, respectively, p ≤ 0.0001, and at center 2 were 83.3%, 33.3%, and 33.3%, p = 0.006. MAPI, which is based on a pre‐implantation biopsy, demonstrated similar predictive and outcome results from both centers. As expanded criteria donors (ECD) criteria have redefined marginal kidneys, MAPI has the potential to further define ECD kidneys, increase utilization, and ultimately improve outcomes.