Reactivity of Schiff base-[C,N,S] pincer palladacycles: hydrolysis renders singular trinuclear, tetranuclear, and heteropentanuclear Pd3W2 coordinated complexes.

Treatment of the Schiff base ligands a-f with Li2[PdCl4]/NaAcO in methanol under reflux gave the single nuclear palladacycles 1a-1f, with the metal atom bonded to a terdentate monoanionic [C,N,S] iminic ligand and to a chloride ligand that completes the palladium coordination sphere. Reaction of 1a-1c with silver perchlorate/triphenylphosphine in acetone at room temperature yielded the single nuclear complexes 2a-2c as the perchlorate salts, after substitution of the chloride ligand by a triphenylphosphine. However, reaction of a-c with Na2[PdCl4]/NaAcO in methanol at room temperature also gave compounds 1a-1c albeit contaminated with small amounts of the corresponding free aldehyde (mixture A). Reaction of mixture A with silver perchlorate/triphenylphosphine in acetone at room temperature gave analogously 2a-2c with some of the corresponding free aldehyde (mixture B). Attempts to purify mixtures A and B via recrystallization produced single crystals of 5 and 6 respectively: two serendipitously formed complexes, bearing thiomethyl aniline and/or acetate ligands, and void of aldehyde or iminic residue; the structures contain eight- and six-membered rings of alternating palladium and nitrogen atoms, respectively. To clarify this situation the aniline itself was reacted with palladium(II) acetate or with Na2[PdCl4]; in the latter case after recrystallization a unique behavior is revealed, giving rise to a tetranuclear complex containing a Pd4N4 ring with three differing coordination environments on the palladium atoms. Treatment of 1d with Ph2PCH2PPh2 (dppm)/AgClO4 or with Ph2PCH2(PPh2)W(CO)5/AgClO4 gave 3d, with a mono-coordinated dppm ligand, and 4d, respectively; complex 3d could not be converted into 4d by reaction with W(CO)5(THF). Recrystallization of 4d gave a still further noticeable species, complex 8: a pentanuclear trans-configured heterometallic mixed valent Pd(II)/W(0) linear complex with the palladium atoms supported by two acetate and two thiomethyl aniline bridging ligands. The complexes were fully characterized by microanalysis, IR, 1H, and 31P NMR spectroscopies, as appropriate. The X-ray single-crystal analyses for compounds 1b, 5, 6, 7 and 8 are described.

Sodium valproate treatment reverses endothelial dysfunction in aorta from rabbits with acute myocardial infarction.

Sodium valproate (VPA), a histone deacetylase (HDAC) inhibitor, could be a promising candidate to treat acute myocardial infarction (AMI). In this study, AMI was induced in New Zealand White rabbits by occluding the left circumflex coronary artery for 1 h, followed by reperfusion. The animals were distributed into three experimental groups: the sham-operated group (SHAM), the AMI group and the AMI + VPA group (AMI treated with VPA 500 mg/kg/day). After 5 weeks, abdominal aorta was removed and used for isometric recording of tension in organ baths or protein expression by Western blot, and plasma for the determination of nitrate/nitrite (NOx) levels by colorimetric assay. Our results indicated that AMI induced a reduction of the endothelium-dependent response to acetylcholine without modifying the endothelium-independent response to sodium nitroprusside, leading to endothelial dysfunction. VPA treatment reversed AMI-induced endothelial dysfunction and even increased NO sensitivity in vascular smooth muscle. This response was consistent with an antioxidant effect of VPA, as it was able to reverse the superoxide dismutase 1 (SOD 1) down-regulation induced by AMI. Our experiments also ruled out that the VPA mechanism was related to eNOS, iNOS, sGC and arginase expression or changes in NOx plasma levels. Therefore, we conclude that VPA improves vasodilation by increasing NO bioavailability, likely due to its antioxidant effect. Since endothelial dysfunction was closely related to AMI, VPA treatment could increase aortic blood flow, making it a potential agent in reperfusion therapy that can prevent the vascular damage.

Anatomical sphincteroplasty as a surgical treatment for faecal incontinence: proposal for a global anatomical reconstructive surgical procedure and results from a case series.

The aim of this study is to describe the technical details and clinical and functional results of anatomical sphincteroplasty as a global reconstructive surgery for the treatment of faecal incontinence caused by anal sphincter lesions. This was a prospective, longitudinal study that included patients who underwent the anatomical sphincteroplasty procedure described here to treat complete sphincter damage. We have described the different technical steps in detail. We evaluated the intraoperative and postoperative complications rate, Cleveland Clinic Score (CCS), a modification of the CCS that included soiling (mCCS), the Faecal Incontinence Quality of Life Scale (FIQLS), and patient satisfaction. An endoanal ultrasound and anorectal manometric study were performed in all the patients. Forty-four patients were included with a mean of 40.5 months follow-up. The CCS reduced from 15 to 3.3 points and the mCCS from 18.5 to 4.5 points over the study period; p < 0.001. Excellent or good results were achieved in 93% of cases. Endoanal ultrasounds showed a good sphincter repair in 66% of the cases. Anorectal manometry showed an increase in the mean maximal resting pressure from 27.6 mmHg to 41.7 mmHg and of the maximal squeeze pressure from 57.9 to 93 mmHg (p < 0.001) with respect to the preoperative values. Anatomical sphincteroplasty is a surgical proposal for the global anatomical reconstruction of anal sphincter lesions, even in cases of very severe damage. The procedure is safe and produced excellent clinical and functional results after a medium-term follow-up.

Baiona's Consensus Statement for Fecal Incontinence. Spanish Association of Coloproctology.

Faecal incontinence (FI) is a major health problem, both for individuals and for health systems. It is obvious that, for all these reasons, there is widespread concern for healing it or, at least, reducing as far as possible its numerous undesirable effects, in addition to the high costs it entails. There are different criteria for the diagnostic tests to be carried out and the same applies to the most appropriate treatment, among the numerous options that have proliferated in recent years, not always based on rigorous scientific evidence. For this reason, the Spanish Association of Coloproctology (AECP) proposed to draw up a consensus to serve as a guide for all health professionals interested in the problem, aware, however, that the therapeutic decision must be taken on an individual basis: patient characteristics/experience of the care team. For its development it was adopted the Nominal Group Technique methodology. The Levels of Evidence and Grades of Recommendation were established according to the criteria of the Oxford Centre for Evidence-Based Medicine. In addition, expert recommendations were added briefly to each of the items analysed.

Noncontrast Myocardial Characterization in Acute Myocardial Infarction Using Electron Density Imaging.

PURPOSE: Spectral computed tomography (CT) enables improved tissue characterization, although virtually all research has focused on contrast-enhanced examinations. We hypothesized that changes in myocardial tissue related to acute myocardial infarction (AMI) might potentially be identified without the need for contrast administration using electron density (ED) imaging. PATIENTS AND METHODS: This retrospective observational study involved a small series (n = 15) of patients admitted to our institution with a first AMI without signs of hemodynamic instability and identification of a culprit vessel with invasive coronary angiography during the same admission, who also underwent a noncontrast, low-dose chest CT using a dual-layer spectral CT scanner. Images were assessed in search of dark areas with low density on ED imaging, and the mean percentage ED relative to water (%EDW) was calculated. RESULTS: Using a qualitative approach, ED assessment enabled the identification of 11/15 (73%) affected coronary territories, with a sensitivity of 73% (95% CI: 45; 92%) and a specificity of 87% (95% CI: 69; 96%). AMI segments showed significantly lower ED values than the remote myocardium (103.8 ± 0.8 vs 104.3 ± 0.6 %EDW, P < 0.0001), and a threshold below 103.9 %EDW had a sensitivity of 66% and specificity of 79% for the identification of AMI. In a control group of patients without a history of cardiovascular disease, none had areas with focal reduction of ED following the shape of the myocardial wall. CONCLUSIONS: In our preliminary series, ED imaging showed the potential to enable the identification of myocardial tissue changes related to AMI without iodinated contrast requirement.

Improvement of Vascular Insulin Sensitivity by Ranolazine.

Ranolazine (RN) is a drug used in the treatment of chronic coronary ischemia. Different clinical trials have shown that RN behaves as an anti-diabetic drug by lowering blood glucose and glycosylated hemoglobin (HbA1c) levels. However, RN has not been shown to improve insulin (IN) sensitivity. Our study investigates the possible facilitating effects of RN on the actions of IN in the rabbit aorta. IN induced vasodilation of the abdominal aorta in a concentration-dependent manner, and this dilatory effect was due to the phosphorylation of endothelial nitric oxide synthase (eNOS) and the formation of nitric oxide (NO). On the other hand, IN facilitated the vasodilator effects of acetylcholine but not the vasodilation induced by sodium nitroprusside. RN facilitated all the vasodilatory effects of IN. In addition, IN decreased the vasoconstrictor effects of adrenergic nerve stimulation and exogenous noradrenaline. Both effects were in turn facilitated by RN. The joint effect of RN with IN induced a significant increase in the ratio of p-eNOS/eNOS and pAKT/AKT. In conclusion, RN facilitated the vasodilator effects of IN, both direct and induced, on the adrenergic system. Therefore, RN increases vascular sensitivity to IN, thus decreasing tissue resistance to the hormone, a key mechanism in the development of type II diabetes.

Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes.

OBJECTIVE: Type 2 diabetes (T2D) is linked to metabolic, mitochondrial and inflammatory alterations, atherosclerosis development and cardiovascular diseases (CVDs). The aim was to investigate the potential therapeutic benefits of GLP-1 receptor agonists (GLP-1 RA) on oxidative stress, mitochondrial respiration, leukocyte-endothelial interactions, inflammation and carotid intima-media thickness (CIMT) in T2D patients. RESEARCH DESIGN AND METHODS: Type 2 diabetic patients (255) and control subjects (175) were recruited, paired by age and sex, and separated into two groups: without GLP-1 RA treatment (196) and treated with GLP-1 RA (59). Peripheral blood polymorphonuclear leukocytes (PMNs) were isolated to measure reactive oxygen species (ROS) production by flow cytometry and oxygen consumption with a Clark electrode. PMNs were also used to assess leukocyte-endothelial interactions. Circulating levels of adhesion molecules and inflammatory markers were quantified by Luminex's technology, and CIMT was measured as surrogate marker of atherosclerosis. RESULTS: Treatment with GLP-1 RA reduced ROS production and recovered mitochondrial membrane potential, oxygen consumption and MPO levels. The velocity of leukocytes rolling over endothelial cells increased in PMNs from GLP-1 RA-treated patients, whereas rolling and adhesion were diminished. ICAM-1, VCAM-1, IL-6, TNFα and IL-12 protein levels also decreased in the GLP-1 RA-treated group, while IL-10 increased. CIMT was lower in GLP-1 RA-treated T2D patients than in T2D patients without GLP-1 RA treatment. CONCLUSIONS: GLP-1 RA treatment improves the redox state and mitochondrial respiration, and reduces leukocyte-endothelial interactions, inflammation and CIMT in T2D patients, thereby potentially diminishing the risk of atherosclerosis and CVDs.

An Innovative Structural Rearrangement in Imine Palladacycle Metaloligand Chemistry: From Single-Nuclear to Double-Nuclear Pseudo-Pentacoordinated Complexes.

Treatment of the double nuclear complex 1a, di-µ-cloro-bis[N-(4-formylbenzylidene)cyclohexylaminato-C6, N]dipalladium, with Ph2PCH2CH2)2PPh (triphos) and NH4PF6 gave the single nuclear species 2a, 1-N-(cyclohexylamine)-4-N-(formyl)palladium(triphos)(hexafluorophasphate). Reaction of 2a with Ph2PCH2CH2NH2 in refluxing chloroform via a condensation reaction of the amine and formyl groups to produce the C=N double bond, gave 3a, 1-N-(cyclohexylamine)-4- N-(diphenylphosphinoethylamine)palladium(triphos)(hexafluorophasphate); a potentially bidentate [N,P] metaloligand. However, attempts to coordinate a second metal by treatment of 3a with [PdCl2(PhCN)2] were to no avail. Notwithstanding, complexes 2a and 3a left to stand in solution spontaneously self-transformed to give in either case the double nuclear complex 10, 1,4-N,N-terephthalylidene(cyclohexilamine)-3,6-[bispalladium(triphos)]di(hexafluorophosphate), after undergoing further metalation of the phenyl ring, then bearing two mutually trans [Pd(Ph2PCH2CH2)2PPh)-P,P,P] moieties: an unprecedented and serendipitous result indeed. On the other hand, reaction of the double nuclear complex 1b, di-µ-cloro-bis[N-(3-formylbenzylidene)cyclohexylaminato-C6, N]dipalladium, with Ph2PCH2CH2)2PPh (triphos) and NH4PF6 gave the single nuclear species 2b, 1-N-(cyclohexylamine)-4-N-(formyl)palladium(triphos)(hexafluorophasphate), Treatment of 2b with H2O/glacial MeCOOH gave cleavage of the C=N double bond and of the Pd···N interaction, yielding 5b, isophthalaldehyde-6-palladium(triphos)hexafluorophosphate, which then reacted with Ph2P(CH2)3NH2 to yield complex 6b, N,N-(isophthalylidene(diphenylphosphinopropylamine)-6-(palladiumtriphos)di(hexafluorophosphate), with two pairs of non-coordinated nitrogen and phosphorus donor atoms. Treatment of 6b with [PdCl2(PhCN)2], [PtCl2(PhCN)2], or [PtMe2(COD)] gave the new double nuclear complexes 7b, 8b and 9b, palladiumdichloro-, platinumdichloro- and platinumdimethyl[N,N-(isophthalylidene(diphenylphosphinopropylamine)-6-(palladiumtriphos)(hexafluorophosphate)-P,P], respectively, showing the behavior of 6b as a palladated bidentate [P,P] metaloligand. The complexes were fully characterized by microanalysis, IR, 1H, and 31P NMR spectroscopies, as appropriate. The X-ray single-crystal analyses for compounds 10 and 5b have been previously described as the perchlorate salts by JM Vila et al.

Validación de la resonancia magnética pélvica como método de elección para determinar la distancia al margen anal en el cáncer de recto / Validation of pelvic magnetic resonance imaging as the method of choice to determine the distance to the anal margin in rectal cancer

Introducción: La altura exacta del tumor en el recto y sus relaciones anatómicas contribuyen a determinar la estrategia terapéutica multidisciplinar basada en la combinación de radio-quimioterapia y cirugía radical. Nuestro objetivo es valorar cuál es el método diagnóstico más preciso en la medición preoperatoria de la distancia al margen anal, y si la resonancia magnética pélvica (RM) puede sustituir a los métodos instrumentales clásicos. Métodos: Estudio prospectivo de precisión diagnóstica entre colonoscopia (CF), rectoscopia rígida (RRp) y RM en pacientes con indicación de cirugía radical. La RRp intraoperatoria fue considerada la prueba de referencia. Se analizaron las correlaciones entre las distintas técnicas y su coeficiente de determinación, así como el coeficiente de correlación intraclase y el grado de acuerdo entre los distintos test. Resultados: Se incluyeron 96 pacientes con edad media (DE) de 68 (14,1) años y predominio de varones (65%). Un 72% recibió tratamiento neoadyuvante. La distancia media al margen anal, medida mediante CF=103,5mm, fue significativamente mayor al resto, que obtuvieron valores similares: RRp=81,1, RM=77,4, RRp intraoperatoria=82,9mm (p<0,001). Se objetivó una significativa correlación intraclase y hubo un elevado acuerdo entre todas las mediciones pre e intraoperatorias a excepción de la realizada mediante CF, que sobreestimó el resultado. La RM aportó información más individualizada y precisa. Conclusiones: Existe variabilidad entre los métodos de medición, siendo la colonoscopia el menos fiable. La RM ofrece valores objetivos, comparables, precisos e individualizados que pueden sustituir a los obtenidos por RR en tumores de cualquier localización del recto. (AU)

Introduction: Distance from anal verge of rectal tumors and their anatomical relationships contribute to determine the multidisciplinary therapeutic strategy based on the combination of radio-chemotherapy and radical surgery. Our aims are to investigate which is the most accurate method for the preoperative measuring of the distance from the anal verge in rectal tumors and if the pelvic MRI can substitute the classical instrumental methods. Methods: Prospective study of diagnostic precision between flexible colonoscopy (FC), preoperative rigid rectosigmoidoscopy (pRR) and pelvic MRI in patients scheduled to radical surgery. Rigid intraoperative rectoscopy (iRR) was considered the reference test. The correlations between the different techniques and their determination coefficient as well as the intraclass correlation coefficient and the degree of agreement between the different tests were analyzed. Results: 96 patients (65% males), mean age (SD): 68 (14.1) years were included. 72% received neoadjuvant treatment. The mean distance to the anal margin measured by FC=103.5mm, was significantly greater than others, which had similar values: pRR=81.1; MRI=77.4; iRR=82.9mm (P<.001). A significant intraclass correlation was observed and there was high agreement between all pre- and intraoperative measurements except for the performed by FC, which overestimated the results. MRI provided more individualized and accurate information. Conclusions: There is variability between the measurement methods, being colonoscopy the least reliable. MRI offers objective, comparable, accurate and individualized values that can replace those obtained by pRR for tumors of any location in the rectum. (AU)

Cerium dioxide nanoparticles modulate antioxidant defences and change vascular response in the human saphenous vein.

Nanoparticles have a promising future in biomedical applications and knowing whether they affect ex vivo vascular reactivity is a necessary step before their use in patients. In this study, we have evaluated the vascular effect of cerium dioxide nanoparticles (CeO2NPs) on the human saphenous vein in response to relaxing and contractile agonists. In addition, we have measured the protein expression of key enzymes related to vascular homeostasis and oxidative stress. We found that CeO2NPs increased expression of both SOD isoforms, and the consequent reduction of superoxide anion would enhance the bioavailability of NO explaining the increased vascular sensitivity to sodium nitroprusside in the presence of CeO2NPs. The NOX4 reduction induced by CeO2NPs may lead to lower H2O2 synthesis associated with vasodilation through potassium channels explaining the lower vasodilation to bradykinin. In addition, we showed for the first time, that CeO2NPs increase the expression of ACE2 in human saphenous vein, and it may be the cause of the reduced contraction to angiotensin II. Moreover, we ruled out that CeO2NPs have effect on the protein expression of eNOS, sGC, BKca channels and angiotensin II receptors or modify the vascular response to noradrenaline, endothelin-1 and TXA2 analogue. In conclusion, CeO2NPs show antioxidant properties, and together with their vascular effect, they could be postulated as adjuvants for the treatment of cardiovascular diseases.

Facilitation of Insulin Effects by Ranolazine in Astrocytes in Primary Culture.

Ranolazine (Rn) is a drug used to treat persistent chronic coronary ischemia. It has also been shown to have therapeutic benefits on the central nervous system and an anti-diabetic effect by lowering blood glucose levels; however, no effects of Rn on cellular sensitivity to insulin (Ins) have been demonstrated yet. The present study aimed to investigate the permissive effects of Rn on the actions of Ins in astrocytes in primary culture. Ins (10-8 M), Rn (10-6 M), and Ins + Rn (10-8 M and 10-6 M, respectively) were added to astrocytes for 24 h. In comparison to control cells, Rn and/or Ins caused modifications in cell viability and proliferation. Rn increased protein expression of Cu/Zn-SOD and the pro-inflammatory protein COX-2 was upregulated by Ins. On the contrary, no significant changes were found in the protein expression of NF-κB and IκB. The presence of Rn produced an increase in p-ERK protein and a significant decrease in COX-2 protein expression. Furthermore, Rn significantly increased the effects of Ins on the expression of p-AKT, p-eNOS, p-ERK, Mn-SOD, and PPAR-γ. In addition, Rn + Ins produced a significant decrease in COX-2 expression. In conclusion, Rn facilitated the effects of insulin on the p-AKT, p-eNOS, p-ERK, Mn-SOD, and PPAR-γ signaling pathways, as well as on the anti-inflammatory and antioxidant effects of the hormone.

Cyclometallated Palladium(II) Complexes: An Approach to the First Dinuclear Bis(iminophosphorane)phosphane-[C,N,S] Metallacycle.

Treatment of bis(iminophosphorane)phosphane ligands 2a-2e with Li2PdCl4 gave a set of novel diphosphane-derived complexes bearing two metallacycle rings, each one enclosing a P=N double bond: the unprecedented bis(iminophosphorane)phosphane-[C,N,S] palladacycles. In the case of the ligand derived from bis(diphenylphosphino)methane, 2a, both the single and the double palladacycle complexes were obtained. Reaction of 3a with bis(diphenylphosphino)ethane did not yield the expected product with the diphosphane bonded to both palladium atoms, but rather the novel coordination compound 5. The crystal structures of 3c and 5 are described.

Cyclometallated Platinum(II) Complexes with Small Crown Ether Rings: Appropriate Choice of the Bridging Diphosphane to Coordinate Potassium Cations.

This account reports the synthesis and structural characterization of the first cyclometallated platinum(II) complex that coordinates a potassium cation in a sandwich arrangement via two 15-crown-5 ether rings within the same molecule. The cooperation of the two small crown ether moieties allows the entrapment of the non-ideal potassium ion. The reaction of the parent thiosemicarbazone ligand 3,4-(C8H16O5)C6H3C(Me)=NN-(H)C(=S)NHMe, 1, containing the crown ether ring, with K2[PtCl4], or alternatively with PtCl2(DMSO)2, and subsequent treatment with the diphosphanes Ph2PCH2PPh2 (dppm) and Ph2PC(=CH2)PPh2 (vdpp) produced the double nuclear platinacycles 3a, 3b, and 4, probably via formation of the 2a and 2b intermediates. Complex 3a with the K+ cation in a sandwich coordination was slightly mixed with 3b lacking any K+. Alternatively, reaction of 1 with K2[PtCl4] or with PtCl2(DMSO)2 followed by the diphosphane Ph2PC(=CH2)PPh2 (vdpp) only gave the dinuclear phosphane-bridged compound 4; this highlights the importance of choosing the right diphosphane ligand. Density functional theory calculations (B3LYP-D3/LANL2DZ-ECP-6.311++G**) revealed similar affinities for both dppm and vdpp derivatives to coordinate potassium cations. Crystal structure analysis was performed for compounds 3a and 4.

Ductal carcinoma in situ of the male breast: clinical radiological features and management in a cancer referral center.

PURPOSE: To present an overview of the management of male patients with Ductal Carcinoma In Situ of the breast (male DCIS). METHODS: We retrospectively studied all male patients with a diagnosis of pure DCIS from January 1999 to December 2018: 20 patients were identified in our cancer referral center. We collected data regarding clinical presentation, age of onset, radiological features, receptor status of the neoplasm, histological type, and the follow-up of those patients. RESULTS: The median age was 62 years (range 21-80). All patients underwent surgery, in 15/20 (75%) cases a mastectomy was carried out. Two patients (10%) underwent endocrine treatment and 1/20 (5%) underwent radiotherapy. The receptor status for 15/20 patients was documented: 13/15 patients were ER+/Pr+. In 3 cases the Ki 67% was positive (i.e., > 20%). All cases were negative for Her2. The median follow-up time was 9.0 years (IQR 4.0-13.7). Only one patient had an ipsilateral recurrence with the finding of an infiltrating carcinoma in the same breast after 14 years. The 5-year disease-free survival was 92.9%. CONCLUSION: Pure DCIS in men is an extremely rare disease: proper diagnosis and management allow an excellent prognosis.

Validation of pelvic magnetic resonance imaging as the method of choice to determine the distance to the anal margin in rectal cancer.

INTRODUCTION: Distance from anal verge of rectal tumours and their anatomical relationships contribute to determine the multidisciplinary therapeutic strategy based on the combination of radio-chemotherapy and radical surgery. Our aims are to investigate which is the most accurate method for the preoperative measuring of the distance from the anal verge in rectal tumours and if the pelvic MRI can substitute the classical instrumental methods. METHODS: Prospective study of diagnostic precision between flexible colonoscopy (FC), preoperative rigid rectosigmoidoscopy (pRR) and pelvic MRI in patients scheduled to radical surgery. Rigid intraoperative rectoscopy (iRR) was considered the reference test. The correlations between the different techniques and their determination coefficient as well as the intraclass correlation coefficient and the degree of agreement between the different tests were analyzed. RESULTS: 96 patients (65% males), mean age (SD): 68 (14.1) years were included. 72% received neoadjuvant treatment. The mean distance to the anal margin measured by FC = 103.5 mm, was significantly greater than others, which had similar values: pRR = 81.1; MRI = 77.4; iRR = 82.9 mm (P < .001). A significant intraclass correlation was observed and there was high agreement between all pre- and intraoperative measurements except for the performed by FC, which overestimated the results. MRI provided more individualized and accurate information. CONCLUSIONS: There is variability between the measurement methods, being colonoscopy the least reliable. MRI offers objective, comparable, accurate and individualized values that can replace those obtained by pRR for tumours of any location in the rectum.

Anatomic sphincteroplasty with combined reconstruction of internal and external anal muscles in the anal incontinence surgical treatment.

Several groups studying the results of the classic sphincteroplasty show improvement of 75% of patients treated in a short-term follow-up, with a worsening of this data in the long-term follow-up down to an improvement of 50% of the patients. Some other groups published more optimistic results, showing an 80% success rate without any deterioration of the technique over time after introducing a separate repair of the internal and external muscles. We think that the introduction of some modifications in the classic technique, named "Anatomic sphincteroplasty with combined reconstruction of external and internal anal sphincter muscles" may obtain very good clinical and anorectal manometric results both in a short and mid-term follow-up. In addition, increasing the pressive length in the anal canal may contribute to maintain more stable results over time.

Imine Palladacycles: Synthesis, Structural Analysis and Application in Suzuki-Miyaura Cross Coupling in Semi-Aqueous Media.

Treatment of the imines a-c with palladium(II) acetate in acetic acid yielded the µ-acetate dinuclear complexes 1a-c, which readily reacted with sodium chloride or bromide to provide µ-halide analogues. The reaction of the latter with nitrogen, phosphorus and oxygen donor nucleophiles yielded new imine palladacycles following the cleavage of the Pd2X2 unit. The complexes were fully characterized by microanalysis, 1H, 13C and 31P NMR spectroscopies, as appropriate. The compounds were applied as catalysts in the Suzuki-Miyaura coupling reaction in aqueous and semi-aqueous media.

Deleterious effects of levamisole, a cocaine adulterant, in rabbit aorta.

Levamisole, a veterinary anthelmintic drug, is one of the most widely used and dangerous cocaine adulterants. Like cocaine, levamisole acutely blocks noradrenaline reuptake but with much less potency, although its vascular effects are not well known. In this study, we evaluated the vascular effects of levamisole and cocaine in rabbit aortic rings used for isometric recording of tension in organ baths and protein expression by western blot. Our results indicated that levamisole (10-5-10-3 M) induced a concentration-dependent relaxation in rings precontracted with noradrenaline (10-7-3 × 10-7 M). Furthermore, it reduced the contractile response to phenylephrine (10-9-3 × 10-5 M) that was not modified by cocaine (10-5-10-4 M), and reduced α1-adrenergic receptor expression. Levamisole (10-6-10-4 M) produced a potentiation of the electrical field stimulation that was not further enhanced by the combination of both drugs. However, high concentrations of levamisole (10-3 M) abolished adrenergic neurotransmission whether administered alone or with cocaine (10-4 M). In addition, levamisole (10-5-10-3 M) also decreased endothelium-dependent relaxation to acetylcholine that was not further impaired by cocaine (10-4 M), and that was partially reversed by superoxide dismutase (SOD, 200 U/ml). These results demonstrate that levamisole has a dual effect on the adrenergic system, and its effects are independent of the presence of cocaine. At lower concentrations, it enhances the contractile sympathetic response by blocking presynaptic α2-adrenergic receptors, while at high concentrations, the effect of the antagonism of α1-adrenergic receptor prevails. In addition, levamisole induces endothelial dysfunction by reducing NO bioavailability, and this effect could be in part mediated by oxidative stress.

LONG-TERM EVOLUTION OF CONTINENCE AND QUALITY OF LIFE AFTER SPHINCTEROPLASTY FOR OBSTETRIC FECAL INCONTINENCE.

PURPOSE: Evaluate the long-term evolution of continence and patient's quality of life after surgical treatment for obstetric fecal incontinence. METHODS: A prospective longitudinal study was conducted including consecutive patients who underwent sphincteroplasty for severe obstetric fecal incontinence. The first phase analyzed changes in continence and impact on quality of life. The second phase studied the long-term evolution reevaluating the same group of patients six years later. Degree of fecal incontinence was calculated using the Cleveland Clinic Score. Quality of life assessment was carried out with the Fecal Incontinence Quality of Life Scale. RESULTS: 35 patients with median age of 55 (range, 28-73) completed the study. Phase One Results: After a postoperative follow-up of 30 months (4-132), Cleveland Clinic Score had improved significantly from a preoperative of 15.7 ± 3.1 to 6.1 ± 5 (p <0.001). Phase Two Results: median follow-up in phase two was 110 months (76- 204). The Cleveland Clinic Score lowered to 8.4 ± 4.9 (p = 0.04). There were no significant differences between phases one and two in terms of quality of life: lifestyle (3.47 ± 0.75 vs. 3.16 ± 1.04), coping/behavior (3.13 ± 0.83 vs 2.80 ± 1.09), depression/self-perception (3.65 ± 0.80 vs 3.32 ± 0.98) and embarrassment (3.32 ± 0.9 vs 3.12 ± 1). CONCLUSION: Sphincteroplasty offers good short-medium term outcomes in continence and quality of life for obstetric fecal incontinence treatment. Functional clinical results deteriorate over time but did not impact on patients' quality of life.