Management of Inflammatory Aortic Aneurysms - A Scoping Review.

OBJECTIVE: Inflammatory abdominal aortic aneurysms (InflAAAs) account for 5 - 10% of aortic aneurysms and are characterised by retroperitoneal fibrosis. Diagnosis is often delayed, and doubts remain about the optimal management strategy. This scoping review describes the current state of knowledge on InflAAAs. METHODS: Medline, PubMed, EMBASE, and Scopus were searched for relevant studies that evaluated the diagnosis and treatment of InflAAAs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was followed. RESULTS: Fifty-seven papers were selected (low level of evidence), which included 1 554 patients, who were mostly male and heavy smokers. A triad of chronic abdominal or back pain, weight loss, and elevated inflammatory markers was highly suggestive of the diagnosis but rarely present, and fever was noted only randomly. A mantle sign was seen on computed tomography angiography (CTA) in 73 - 100% of patients. Open surgical repair (OSR) and endovascular aortic aneurysm repair (EVAR) was reported in 1 376 and 178 patients, respectively. OSR was associated with significant iatrogenic bowel (n = 22), urinary tract system (n = 7), venous (n = 30), pancreatic (n = 6), and splenic (n = 5) injuries, while EVAR was associated with lower 30 day mortality (0 - 5% vs. 0 - 32%). One and two year mortality rates were similar between the two treatment modalities (0 - 20% and 0 - 36%, respectively). EVAR was more often associated with post-operative progression of inflammation (17% vs. 0.4%), and a higher frequency of persistent hydronephrosis (> 50%) and limb occlusion (20%). Used in < 10% of patients, corticosteroids led to complete pain relief and a reduction in peri-aortic inflammation within 6 - 18 months. CONCLUSION: InflAAAs are characterised by non-specific symptoms, with the mantle sign on CTA being pathognomonic. Corticosteroids may be considered a basic treatment that all patients should receive initially. Low quality data indicate that EVAR (vs. OSR) is associated with fewer intra-operative complications and lower peri-operative mortality but more late fibrosis related adverse events. International multicentre registries are required to gather more insights into this challenging pathology.

Thrombosis of abdominal aorta in congenital afibrinogenemia: case report and review of literature.

Thrombotic events in congenital hypo-afibrinogenemia have been rarely reported, either in association or not with replacement therapy or thrombotic risk factors. We describe clinical findings and management of thrombosis of abdominal aorta with peripheral embolism in a patient with congenital afibrinogenemia. A review of arterial thrombosis in inherited hypo-afibrinogenemia was also performed. The patient with a severe bleeding history requiring prophylaxis with fibrinogen concentrates (FC) was admitted for ischaemia of the 4th right toe. An angio-CT of abdominal aorta showed a thrombosis from the origin of renal arteries to the carrefour with a distal floating part. No thrombotic risk factors were found; a previous traumatic lesion of aortic wall might have triggered the thrombus formation, whereas the role of FC prophylaxis remains uncertain. The patient was successfully treated with FC, enoxaparin followed by fondaparinux, and low-dose aspirin without bleeding or thrombosis recurrence. After 2 years, aortic thrombus was almost completely recovered. Sixteen hypo/afibrinogenemia patients with arterial thrombosis were found in Literature, showing that thrombosis often occurs at a young age, involves large vessels, its recurrence is not unusual, and therapeutic strategy is not defined yet. Our therapeutic approach was effective and also safe, but further studies are needed to improve the knowledge of pathogenesis and the anti-thrombotic management in this peculiar setting.

Selective crossectomy combined with mechanochemical ablation in the treatment of great saphenous vein insufficiency: Early results of a single center experience.

BACKGROUND: Selective crossectomy and mechanochemical ablation (MOCA) of great saphenous vein (GSV) have been used, for years, individually in the treatment of chronic venous insufficiency. In this paper, we focus on the advantages of a combination of the two techniques, in order to prevent complications and recurrence. METHODS: A preoperative clinical and instrumental screening phase was conducted for the purpose of dividing patients into three groups: "Saph+Cross" group (51/139 patients) underwent saphenectomy and crossectomy; "MOCA" group (44/139 patients) underwent MOCA of GSV with Flebogrif® device; "MOCA + Cross" group (44/139 patients) subjected to both MOCA and crossectomy procedures.Recurrence rate, defined as total recanalization of GSV and/or onset of neosaphena and/or new varicose veins, was used as a primary outcome. Secondary outcomes were procedural time and intra- and post-procedural complications. RESULTS: We conducted a 1-, 6-, and 12-month follow-up with Duplex scan. The recurrence rates were 3.9%, 21.8%, and 4.5% for "Saph+Cross," "MOCA," and "MOCA+Cross," respectively, with a significant difference for the comparison between "MOCA" and "Saph+Cross" (MOCA vs Saph+Cross: OR 5.35, CI95% [0.98; 54.6], p-value .040).The sub-analysis of primary outcome highlighted a lower recanalization rate of GSV when combining the crossectomy with MOCA procedure (2.2% MOCA+Cross vs 15.9% MOCA; 0.12 OR, [0.002; 1.02] CI95%, p-value .029).Among the secondary outcomes, "MOCA" showed a shorter procedural time than the other groups (Saph+Cross: 51.3 ± 11.4; MOCA: 45.1 ± 7.5; MOCA+Cross: 50.4 ± 10; p-value .027). No significant differences were noted in terms of intra- and post-procedural complications. CONCLUSIONS: The results showed that patients treated with saphenectomy and crossectomy have a lower recurrence rate compared to MOCA alone and MOCA + crossectomy procedures.The association of crossectomy with MOCA significantly reduces the recanalization rate of GSV, and it is also characterized by a higher free survival from recurrence (SSF) than with MOCA alone.

A doppel alpha-helix peptide fragment mimics the copper(II) interactions with the whole protein.

The doppel protein (Dpl) is the first homologue of the prion protein (PrP(C)) to be discovered; it is overexpressed in transgenic mice that lack the prion gene, resulting in neurotoxicity. The whole prion protein is able to inhibit Dpl neurotoxicity, and its N-terminal domain is the determinant part of the protein function. This region represents the main copper(II) binding site of PrP(C). Dpl is able to bind at least one copper ion, and the specific metal-binding site has been identified as the histidine residue at the beginning of the third helical region. However, a reliable characterization of copper(II) coordination features has not been reported. In a previous paper, we studied the copper(II) interaction with a peptide that encompasses only the loop region potentially involved in metal binding. Nevertheless, we did not find a complete match between the EPR spectroscopic parameters of the copper(II) complexes formed with the synthesized peptide and those reported for the copper(II) binding sites of the whole protein. Herein, the synthesis of the human Dpl peptide fragment hDpl(122-139) (Ac-KPDNKLHQQVLWRLVQEL-NH(2)) and its copper(II) complex species are reported. This peptide encompasses the third alpha helix and part of the loop linking the second and the third helix of human doppel protein. The single-point-mutated peptide, hDpl(122-139)D124N, in which aspartate 124 replaces an asparagine residue, was also synthesized. This peptide was used to highlight the role of the carboxylate group on both the conformation preference of the Dpl fragment and its copper(II) coordination features. NMR spectroscopic measurements show that the hDpl(122-139) peptide fragment is in the prevailing alpha-helix conformation. It is localized within the 127-137 amino acid residue region that represents a reliable conformational mimic of the related protein domain. A comparison with the single-point-mutated hDpl(122-139)D124N reveals the significant role played by the aspartic residue in addressing the peptide conformation towards a helical structure. It is further confirmed by CD measurements. Potentiometric titrations were carried out in aqueous solutions to obtain the stability constant values of the species formed by copper(II) with the hDpl peptides. Spectroscopic studies (EPR, NMR, CD, UV/Vis) were performed to characterize the coordination environments of the different metal complexes. The EPR parameters of the copper(II) complexes with hDpl(122-139) match those of the previously reported copper(II) binding sites of the whole hDpl. Addition of the copper(II) ion to the peptide fragment does not alter the helical conformation of hDpl(122-139), as shown by CD spectra in the far-UV region. The aspartate-driven preorganized secondary structure is not significantly modified by the involvement of Asp124 in the copper(II) complex species that form in the physiological pH range. To elaborate on the potential role of copper(II) in the recently reported interaction between the PrP(C) and Dpl, the affinity of the copper(II) complexes towards the prion N terminus domain and the binding site of Dpl was reported.

Ternary copper(II) complexes with 1,10­phenanthroline and various aminoacidates: A spectroscopic and voltammetric study in aqueous solution.

Ternary copper(II) complexes with 1,10­phenanthroline and the aminoacids l­arginine, l­aspartic acid, l­histidine, l­glutamic acid, l­glutamine, l­leucine, l­lysine, l­methionine, l­phenylalanine, l­tryptophan, l­tyrosine, l­valine, were studied in aqueous solution by means of UV-Vis-NIR spectrophotometry, EPR spectroscopy either at room or at low temperatures, and Square Wave Voltammetry. From the experimental data it is possible to conclude that most of these ternary complexes show a pseudo-octahedral geometry with a CuN3O in plane chromophore and two oxygen atoms coming from water molecules perpendicularly bound to the equatorial plane. An exception to this general behaviour is given by the ternary copper(II) complex with 1,10­phenanthroline and histidine at pH value near the neutrality because of the terdentate nature of histidine when it coordinates by means of its histamine-like mode. In this case, evidence for a probable square-based pyramidal stereochemistry is given in support. At pH values around 5 the histidine behaves as bidentate ligand coordinating by its glycine-like mode, so as the copper(II) ternary complex with 1,10­phenathroline shows the pseudo-octahedral geometry found for all the ternary complexes with the other aminoacids. Moreover the ternary complex species with histidine at pH 5 and 7 are in equilibrium with each other as a function of the aqueous solution pH value and the temperature. In fact, the examination of low temperature EPR spectra at pH near 7 revealed not only a square-based pyramid complex but also products of decomposition. These results were also confirmed by the trend found in the formal redox potentials by the voltammetric measurements on many of these ternary complexes.

Simple and mixed complexes of copper(II) with 8-hydroxyquinoline derivatives and amino acids: Characterization in solution and potential biological implications.

Copper(II) complexes with 8-hydroxyquinoline (8-HQ) and two 8-HQ derivatives, namely clioquinol (CQ) and 5,7-dichloro-2-[(dimethylamino)methyl]quinolin-8-ol (PBT2), were investigated in organic and, where feasible, in aqueous solutions. This class of compounds is of particular interest in neurological disorders since they may act as metal-protein attenuating compounds and may help redistributing metal ions and restoring intracellular metal reserves, which are often perturbed in neurological patients. Several techniques, like potentiometry, UV-Vis absorption, electron paramagnetic resonance (EPR), cyclic voltammetry and electrospray ionisation-mass spectrometry (ESI-MS), were used to obtain information on both the formation of copper(II) complexes in solution as well as on the structure of their species. Multi-wavelength treatment of UV-Vis data clearly indicated the formation of both [Cu(PBT2)]+ and [Cu(PBT2)2] species; the speciation was also supported by ESI-MS data. The EPR results showed that the mono- and bis-copper(II) complexes with PBT2 have square-based pyramidal structures while the bis-copper (II) complexes with CQ or 8-HQ have square-planar o pseudo-octahedral geometries. The formation of copper(II) ternary complexes with 8-HQ, CQ and PBT2 and some selected neurotransmitters (glycine, glutamate and histidine) is also reported. Except for the copper(II) ternary complex with PBT2 and His, almost all ternary complexes have molecular geometries, which are not different from those of the bis-complexes. Interestingly the ternary copper(II) complexes, containing CQ, 8-HQ and PBT2 and glycine, glutamate or histidine turned out to be more soluble in aqueous solution than their binary complexes with parent 8-HQ derivatives; the copper(II) complexes can also be reduced more easily than their parent bis-complexes.

Pancreas Transplantation at a Single Latin-American Center; Overall Results with Type 1 and Type 2 Diabetes Mellitus.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) has become the treatment of choice for type 1 diabetes mellitus (T1DM) patients with chronic renal failure. Type 2 diabetes mellitus (T2DM), was once considered to be a contraindication for pancreas transplantation; however, it has been accepted as a new indication, under strict criteria. Although favorable results have increase the indication for T2DM in developed countries, there have been no reports of long-term results for this indication from Latin American centers. METHODS: From April 2008 to March 2016, patients receiving SPK or pancreas transplant alone (PTA) for T2DM were included and compared with T1DM recipients. Variables were compared between groups with the use of χ2 and t tests; Kaplan-Meier with log rank was used for patient and graft survivals; P < .05 was considered to be significant. RESULTS: A total of 45 SPK and 1 PTA were performed, 35 (76.1%) for T1DM and 11 (24.5%) for T2DM. Mean pre-transplantation C-peptide was significantly higher in the T2DM group (P = .01); HbA1c was higher in the T1DM group (P = .03). No differences were found in weight, body mass index, and pre-transplantation glycemia. Patient survivals for T1DM recipients were 88.2% and 84.8% at 1 and 5 years, respetively, versus 100% and 74.1% for T2DM recipients (P = .87). CONCLUSIONS: Our initial prospective experience in a single Latin American center showed that medium- and long-term outcomes for T1DM and T2DM individuals receiving pancreas transplants are similar, under strict selection criteria.

Copper ion interaction with the RNase catalytic site fragment of the angiogenin protein: an experimental and theoretical investigation.

The angiogenin protein (Ang) is a member of the vertebrate-specific secreted ribonucleases and one of the most potent angiogenic factors known. Ang is a normal constituent of human plasma and its concentration increases under some physiological and pathological conditions to promote neovascularization. Ang was originally identified as an angiogenic tumour factor, but its biological activity has been found to extend from inducing angiogenesis to promoting cell survival in different neurodegenerative diseases. Ang exhibits weak ribonucleolytic activity, which is critical for its biological functions. The RNase catalytic sites are two histidine residues, His-13 and His-114, and the lysine Lys-40. Copper is also an essential cofactor in angiogenesis and influences angiogenin's biological properties. The main Cu(ii) anchoring site of Ang is His-114, where metal binding inhibits RNase activity of the protein. To reveal the Cu(ii) coordination environment in the C-terminal domain of the Ang protein, we report on the characterization, by means of potentiometric, voltammetric, and spectroscopic (CD, UV-Vis and EPR) methods and DFT calculations, of Cu(ii) complexes formed with a peptide fragment including the Ang sequence 112-117 (PVHLDQ). Potentiometric titrations indicated that [CuLH-2] is the predominant species at physiological pH. EPR, voltammetric data and DFT calculations are consistent with a CuN3O2 coordination mode in which a distorted square pyramidal arrangement of the peptide was observed with the equatorial positions occupied by the nitrogen atoms of the deprotonated amides of the Asp and Leu residues, the δ-N atom of histidine and the oxygen atom of the aspartic carboxylic group. Moreover, two analogous peptides encompassing the PVHLNQ and LVHLDQ sequences were also characterized by using thermodynamic, spectroscopic and DFT studies to reveal the role they play in Cu(ii) complex formation by the carboxylate side chain of the Asp and Pro residues, a known breaking-point in metal coordination.

Solution equilibria and the X-ray structure of Cu(ii) complexation with 3-amino-N-(pyridin-2-ylmethyl)propanamide, a pseudo-mimic of human serum albumin.

Copper complexes have anti-inflammatory activity in the treatment of inflammation associated with rheumatoid arthritis (RA). The preferred route of administration is through the skin, so the rate of dermal absorption and bioavailability of copper is important. Based on previous studies, 3-amino-N-(pyridin-2-ylmethyl)-propanamide, [H(56)NH2], was designed as a potential chelator of copper. The stability constant measurements revealed that MLH-1 is the most stable species at the physiological pH of 7.4. The X-ray crystal structure of this species was solved and copper was found in a rectangular pyramidal geometry. The ligand occupied three coordination sites while bridging chloride linked copper ions together in a chain. The ligand bound to the metal ion through the pyridyl nitrogen, the amide nitrogen and the terminal amino group. Spectroscopic studies confirmed that this structure persisted in aqueous solution. Octanol/water partition coefficients and Franz cell permeation studies showed that [H(56)NH2] is able to promote the dermal absorption of Cu(ii).

Surveillance Registry of Sirolimus Use in Recipients of Kidney Allografts From Expanded Criteria Donors.

BACKGROUND: The use of expanded criteria donor (ECD) kidneys has increased the overall availability of renal transplants. This study assessed the use of sirolimus in patients receiving Argentina-ECD kidneys. METHODS: This observational, open-label, 1-arm, prospective, longitudinal pilot study was conducted at 8 transplant centers in Argentina. Adults receiving kidney transplants (without pancreas) from ECDs were eligible if they were converted to sirolimus 1 to 36 months' posttransplantation, with sirolimus becoming base therapy within 1 month after conversion. Patients were followed up for 1 year. Outcomes included reasons for conversion, acute rejection, patient and graft survival, graft status, and safety. RESULTS: The intention-to-treat population included 52 patients (mean age, 48.7 years). Calcineurin inhibitor nephropathy (40%) and chronic allograft nephropathy (25%) were the most frequent reasons for conversion. Two acute rejections occurred during follow-up, but no patients experienced graft loss. One patient died during follow-up, and 3 patients died within 1 month of the last sirolimus dose. Levels of serum creatinine and creatinine clearance remained stable from baseline to week 52/53. Mean proteinuria measured in a subset of patients was 0.2 ± 0.2 g/24 hours before conversion and increased to 0.6 ± 1.2 g/24 hours at week 24/25 and 0.5 ± 0.6 g/24 hours at week 52/53. Adverse events were consistent with those in previous conversion trials; the most common were infections and infestations (54%). CONCLUSIONS: This pilot study illustrates the potential benefits of sirolimus in recipients of ECD kidneys in Argentina. Larger, randomized controlled trials are needed to confirm these findings and to clarify the long-term benefits of sirolimus in this patient population.

The value of platelet transfusions as preparation for kidney transplantation.

The role of platelet transfusion as a preparative method for kidney transplantation is still a matter of debate. Two groups of 28 male patients transplanted between 1983 and 1988, paired for age, date of transplant, absence of anti-HLA antibody and immunosuppressive therapy have been compared. Group I was given 5 purified platelet transfusions at 1-week intervals before transplantation. Each transfusion contained 7.6 x 10(6) platelets contaminated by less than 1 leukocyte in 10(5) platelets. Group II received from 3 to 5 whole blood transfusions. In all cases it was a first transplant from cadaveric donors and previously untransfused patients before entering the protocol. No patient in group I developed cytotoxic antibodies. Acute tubular necrosis occurred with the same incidence in group I and in group II but was more severe and longer in group I, requiring hemodialysis in 62.5% and only 22% in group II. ATN was significantly associated with graft loss in group I (P less than 0.05). The total number of rejections and the number of patients undergoing rejection were not significantly different in both groups. However, the intensity of rejection was significantly higher in group I with 41% (21/51) of severe or irreversible rejections versus 9/46 (19.5%) in group II (P less than 0.05). The first rejection occurred significantly earlier in group I than in group II since 75% of the first rejection episodes occurred in the first 10 days versus 38% in group II (P less than 0.02) with a mean delay of 12.8 +/- 3.2 and 19.10 +/- 3.3 days, respectively. Although platelet transfusions are devoid of leukocytes the incidence of CMV infection was not significantly different in both groups: 57% in group I and 68% in group II. Purified platelet transfusions did not induce humoral immunization but lack of sensitization does not imply indefinite graft prolongation. Because platelets do not carry class II antigens, purified platelets transfusions represent a useful model to analyze the role of class I antigens alone in the induction of unresponsiveness in organ transplantation.

Natriuretic effect and changes in renal haemodynamics induced by enalapril in essential hypertension.

The purpose of this study was to evaluate the natriuretic effect and renal haemodynamic changes induced by enalapril in patients with essential hypertension. In a group of 11 patients with mild to moderate hypertension with normal renal function, and on a controlled sodium intake (80 mmol/day), a decrease in systolic and diastolic blood pressure was observed (p less than 0.001) after 16 weeks of enalapril treatment (20 mg/day), without a change in heart rate. An increase in plasma renin activity (p less than 0.05) without changes in serum aldosterone, and a decrease in exchangeable sodium (p less than 0.001) were present at the end of the treatment period. In 10 hypertensive patients also taking a dietary sodium of 80 mmol/day, the renal haemodynamics, humoral changes, and urinary sodium excretion were measured during 4 days of enalapril treatment (20 mg/day). There was an increase in urinary sodium excretion on the 3rd and 4th days of treatment (p less than 0.01). The effective renal plasma flow and fractional sodium excretion increased 72 hours after the beginning of treatment (p less than 0.01); the glomerular filtration rate did not change, and filtration fraction decreased at 72 hours. Mean blood pressure fell 2 hours after the first dose (p less than 0.01), and the maximum drop in intrarenal vascular resistance occurred after 72 hours of treatment (p less than 0.01). Plasma renin activity increased (p less than 0.05) and serum aldosterone decreased (p less than 0.01) 2 hours after the first dose. Thereafter, serum aldosterone increased progressively until it reached values similar to those with placebo at 48 and 72 hours of treatment. Urinary kallikrein fell during the 2nd and 3rd day of treatment (p less than 0.01). It was concluded that the decrease in exchangeable sodium was due to a natriuretic effect of enalapril. This effect presumably results from renal haemodynamic changes due to the reduction of angiotensin II. Other mechanisms, such as the reduction of aldosterone and accumulation of kinins, could be contributory factors.

Molecular Recognition of Amino Acids by Copper(II) Complexes of 6(A),6(X)-Diamino-6(A),6(X)-dideoxy-beta-cyclodextrin (X = B, C, D).

The three regioisomers of beta-cyclodextrin 6-difunctionalized with NH(2) groups (6(A),6(X)-diamino-6(A),6(X)-dideoxy-beta-cyclodextrin, A,X-CDNH(2), X = B, C, or D) were synthesized. Their binary and ternary copper(II) complexes with amino acids were characterized by ESR and electronic spectroscopy. Furthermore, the binary copper(II) complexes were used as eluent in ligand exchange chromatography (LEC), to resolve racemates of unmodified amino acids. HPLC separation of enantiomers of aromatic amino acids was obtained only when the complex [Cu(A,B-CDNH(2))](2+) was used as eluent. The two complexes with the other two regioisomers did not show chiral recognition ability. Circular dichroism (c.d.) spectroscopy studies of the ternary complexes with D- and L-amino acids carried out in the presence and in the absence of 1-adamantanol, suggested a recognition mechanism that involves the cyclodextrin cavity, only in the case of ternary A,B-CDNH(2) complexes.

High Superoxide Dismutase Activity of a Novel, Intramolecularly Imidazolato-Bridged Asymmetric Dicopper(II) Species. Design, Synthesis, Structure, and Magnetism of Copper(II) Complexes with a Mixed Pyrazole-Imidazole Donor Set.

A new dinucleating ligand, 1,5-bis(1-pyrazolyl)-3-[bis(2-imidazolyl)methyl] azapentane (Hbpzbiap), containing pyrazoles and imidazoles has been designed and synthesized. The synthesis and characterization of the copper complexes with the ligand Hbpzbiap and its dehydronated form are described. This study is aimed at modeling the active site of copper-zinc superoxide dismutase (SOD). Single crystals of the imidazolato-bridged complex [Cu(2)(bpzbiap)Cl(3)] (1) and non-imidazolato-bridged complex [Cu(2)(Hbpzbiap)Cl(4)] (2) were obtained and their structures determined by X-ray diffraction. Both structures show two copper centers in two different coordination environments: a distorted square pyramid and a distorted tetrahedron. The Cu-nitrogen bond lengths range from 1.919(4) to 2.039(3) Å and are as expected. The copper-copper distances from 5.566(1) to 6.104(1) Å being only slightly shorter than that found in bovine erythrocyte SOD. Temperature-dependent magnetic susceptibility study of 1 shows antiferromagnetic behavior with -2J = 96 cm(-)(1). From pH-dependent electron paramagnetic resonance and electronic spectra, [Cu(2)(bpzbiap)Cl(3)] has been demonstrated to be stable over a quite wide pH range including the physiological pH values. A low concentration of this complex (1) catalyzes the dismutation of superoxide at biological pH. Voltammetric studies indicate a quasi-reversible redox behavior in aqueous solution at pH 7. These results clearly indicate that complex 1 is a good model for superoxide dismutase.

Crystal and Molecular Structure of the [6-Deoxy-6-[(2-(4-imidazolyl)ethyl)amino]- cyclomaltoheptaose]copper(II) Ternary Complex with L-Tryptophanate. Role of Weak Forces in the Chiral Recognition Process Assisted by a Metallocyclodextrin.

The ternary copper(II) complex of 6-deoxy-6-[(2-(4-imidazolyl)ethyl)amino]cyclomaltoheptaose (CDhm) and L-tryptophanate (L-TrpO(-)) was characterized by ESR and X-ray diffraction. The solid state structure of [Cu(CDhm)(L-TrpO)](+) shows that the aromatic side chain of TrpO(-) is outside the cavity and that the two amino nitrogen atoms, one from the histamine molecule and one from the amino acidate, are in a cis disposition. The two amino nitrogens, the imidazole nitrogen, and the carboxylate oxygen atoms form the base of a square pyramid, which surrounds the copper(II) ion, a water molecule occupying an apical position. Atomic distances suggest for this complex that pi-pi and d-pi interactions could occur in the solid state. Morover, the [Cu(CDhm)(L-TrpO)](+) has a self-assembled structure in which a CDhm molecule behaves as host and as guest. The imidazole and the indole ring are directed into the cavity of an adjacent CDhm molecule from the wider cyclodextrin rim, thus forming a polymeric column structure. ESR spectra were run on the copper(II) ternary complexes with L- or D-tryptophanate and L- or D-alaninate in frozen aqueous solution and on the former pair of enantiomers in the solid state, as well. While in the case of the ternary complex with L- or D-alaninate no differences are observed in their frozen solution spectra, in the case of complexes with TrpO(-) subtle differences are found. These differences, which disappear when excess methanol is used, are ascribed to the presence of weak forces, such as hydrophobic or d-pi interactions.

[Influence of HLA compatibility on cytomegalovirus infection in kidney transplantation]. / Influence de la compatibilité HLA sur l'infection à cytomégalovirus en transplantation rénale.

The influence of HLA A, B, DR on the incidence and symptoms of cytomegalovirus (CMV) infection was investigated in 143 patients who, between October 1st, 1987 and December 31st, 1989, received kidneys from cadaveric donors. Systematic virological monitoring was carried out weekly during the first hospitalization and thereafter at each new hospitalization or in the presence of clinical signs suggestive of viral infection. The diagnosis of CMV was based on positive isolation in blood or urine, or seroconversion, or 4-dilution rise in the anti-CMV antibodies titre. HLA grouping of all recipients was made in the same histocompatibility laboratory. Immunosuppression was obtained with a quadruple therapy consisting of corticosteroids (15 mg/kg before transplantation, then 1 mg/kg for 10 days, then gradually tapering off dosage), azathioprine (2 to 3 mg/day), cyclosporin A (2 mg/kg i.v. followed by an oral dose adjusted to the residual levels) and a randomized treatment with either monoclonal anti-CD3 antibody or anti-thymocyte globulins administered during the first 10 days. The incidence of CMV infection was 56 percent (80/143), with 25 percent of primary infection (20/80). The number of DR compatibilities was found to have a significant influence on the incidence of CMV infection, which rose from 22 to 50 and 65 percent respectively in the group of patients with 2.1 or 0 DR compatibility (P less than 0.02). The degree of B + DR compatibility was also associated with the occurrence of CMV infection, the incidence of which rose from 0 to 36, 59, 43.5 and 71 percent respectively in the group of patients with 4, 3, 2, 1, 0 B + DR compatibility (P less than 0.03). The incidence of primary CMV infection increased with the number of DR incompatibilities, rising from 0 to 29 and 52 percent respectively in the group of patients with 0, 1 or 2 DR incompatibilities. The symptoms and severity of CMV infection were significantly influenced by the degree of DR and B + DR compatibility. Despite a very strong association between graft rejection and CMV infection (P less than 0.000001), no influence of HLA, and particularly DR or B + DR compatibility on the incidence and number of graft rejections could be demonstrated. It is concluded that, under the above-described quadruple therapy, the HLA DR and B + DR compatibility exerts a predominant influence on the occurrence and severity of CMV infection, and that this effect is independent of any action on graft rejection.(ABSTRACT TRUNCATED AT 400 WORDS)

Short- and long-term outcomes of every graft recovered during a multi-organ procurement procedure including the intestine.

BACKGROUND: The development of intestinal transplant (Tx) programs introduces thymoglobulin donor treatment as well as an almost complete warm dissection of the abdominal organs to allocate them to different recipients. Our aim is to assess the reproducibility and feasibility of the surgical technique of multi-organ procurement with the use of thymoglobulin donor pre-treatment and report the short- and long-term outcomes of every graft harvested as part of multi-organ procurement (MTOp), including the intestine. METHODS: Data were collected of all organs harvested from MTOp, including the intestines allocated to our center from March 2006 to July 2011. Data from 92 recipients and 116 organs procured from 29 MTOp were analyzed. Twelve hearts, 2 lungs, and 1 cardio-pulmonary block were transplanted; primary graft dysfunction developed in 4 of the 12 hearts and in the cardio-pulmonary block. RESULTS: The survival rate was 75% and 100% for hearts and lungs, respectively. Nineteen livers, 9 kidney-pancreas, 19 kidneys, and 29 intestines were transplanted. Delayed graft function (DGF) of the pancreas developed in 3 of 9 kidney-pancreas, and the other 3 exhibited DGF of the kidney; 4 of 19 Tx kidneys had DGF. The survival was 84%, 78%, 95%, and 65.5% for livers, kidney-pancreas, kidneys, and intestines, respectively. CONCLUSIONS: Organs procured during MTOp including the intestine can be safely used, increasing organ availability and transplant applicability without compromising allocation, quality, and long-term results of the non-intestinal-procured organs.

First epidemiologic study in Argentina of the prevalence of BK viruria in kidney transplant patients.

BACKGROUND: The worldwide seroprevalence of human BK polyomavirus (BKV) in adults is 80%. About 10%-60% of renal transplant recipients experience BKV infection, nephropathy of the graft may occur in 5% of the cases, and up to 45% lose the graft. The aim of this work was to describe the prevalence of BK viruria during the 1st year after transplantation. METHODS: An epidemiologic multicenter cross-sectional study was carried out in consecutive patients at each site with kidney transplantation from August 2011 to July 2012. Clinically significant viruria was defined as >10(7) copies/mL. Viral DNA was extracted with the use of silica columns. Quantification was performed with the use of real-time polymerase chain reaction with primers that amplify a fragment of the large T-antigen gene and with a specific Taqman-MGB probe for BKV. For each assay, a standard curve with a quantified plasmid was included. RESULTS: Of 402 renal transplant recipients at 18 renal transplant sites, we analyzed 382; median age was 46.33 years, and 46.40% were female. The median of the temporal distribution for urine samples was 153 days. BK virus was detected in 50/382 samples (13%), 18 with values >10(7) copies/mL (4.7%). The median of the distribution of positive values was 123 days and the highest frequency of positive values was in months 3-7. The conditions of recipient older than 34 years and donor older than 41 years were the only ones that showed statistically significant association with BK viruria. No association with any specific immunosuppressive drug was observed. CONCLUSIONS: This is the first multicenter study conducted in Argentina to determine the prevalence of BK viruria in renal transplant recipients. Because of the growing number of the population susceptible to this infection, it is important to register and describe data about its epidemiology and associated risk factors.

Determination of formal redox potentials in aqueous solution of copper(II) complexes with ligands having nitrogen and oxygen donor atoms and comparison with their EPR and UV-Vis spectral features.

Formal redox potentials in aqueous solution were determined for copper(II) complexes with ligands having oxygen and nitrogen as donor atoms. All the chosen copper(II) complexes have well-known stereochemistries (pseudo-octahedral, square planar, square-based pyramidal, trigonal bipyramidal or tetrahedral) as witnessed by their reported spectroscopic, EPR and UV-visible (UV-Vis) features, so that a rough correlation between the measured redox potential and the typical geometrical arrangement of the copper(II) complex could be established. Negative values have been obtained for copper(II) complexes in tetragonally elongated pseudo-octahedral geometries, when measured against Ag/AgCl reference electrode. Copper(II) complexes in tetrahedral environments (or flattened tetrahedral geometries) show positive redox potential values. There is a region, always in the field of negative redox potentials which groups the copper(II) complexes exhibiting square-based pyramidal arrangements. Therefore, it is suggested that a measurement of the formal redox potential could be of great help, when some ambiguities might appear in the interpretation of spectroscopic (EPR and UV-Vis) data. Unfortunately, when the comparison is made between copper(II) complexes in square-based pyramidal geometries and those in square planar environments (or a pseudo-octahedral) a little perturbed by an equatorial tetrahedral distortion, their redox potentials could fall in the same intermediate region. In this case spectroscopic data have to be handled with great care in order to have an answer about a copper complex geometrical characteristics.

Electrochemical characterization of ordered arrays of metallo-porphyrins in aqueous solution.

Metallated meso-tetrakis(N-methyl-4-pyridyl)porphyrin (MTMPyP) and 5,11,17,23-tetrasulfonato-25,26,27,28-tetrakis-(hydroxylcarbonylmethoxy)-calix[4]arene (C(4)TsTc) were used as key components for building up discrete supramolecular entities starting from the formation of the template species MTMPyP:C(4)TsTc (1 : 4, M = Cu, Zn). The stepwise addition of further amount of porphyrin allows the facile non-covalent synthesis of discrete supramolecular entities (2 : 4 and 3 : 4) which can be built up just by programming the right stoichiometric addition of the proper porphyrin. The redox potentials of these supramolecular complexes in aqueous media, as well as those of the parent metalloporphyrins, have been characterized by using square wave voltammetry technique. The use of the simulation procedure leads us to establish the electrochemical steps involved in the redox processes for each supramolecular species, evidencing multistep electron reductions which were not experimentally resolved clearly because of their closeness. The most striking result is that the electrochemistry of each of these supramolecular complexes is different from that of the parent components. This "anomalous" behavior can be explained only considering each of these supramolecular complexes as a unique entity, in which such an internal electronic communication might occur. The formation of the 1 : 4 supramolecular complex produces a negative shift as to the metallated porphyrin redox potentials of about 30 mV. In the case of 2 : 4 and 3 : 4 species, the redox potentials progressively shifts towards more positive values by about 10-15 mV for each complexation step.