Nutritional guidance, monitoring, and supplementation before and after bariatric surgery - Are we doing this correctly?

INTRODUCTION: Background and aims: minimizing nutritional depletions after a Roux-en-Y gastric bypass (RYGB) may improve clinical results in the treatment of obesity. We evaluated nutritional aspects of obese women undergoing RYGB at a reference university hospital with a department specialized in bariatric surgery. Method: based on the Dietary Reference Intakes developed by the Food and Nutrition Council, Institute of Medicine, and the guidelines issued by the American Society for Metabolic and Bariatric Surgery, we assessed the quantitative and qualitative adequacy of nutritional intake, supplementation, and biochemical monitoring of 20 women both before and 3 and 12 months after a RYGB. Data on nutritional intake was obtained by applying different food surveys, quantitatively interpreted by the Virtual Nutri Plus® software and using reference nutritional databases. Results: nutritional intake deficits were already found before the RYGB (p ≤ 0.05). These worsened postoperatively (p ≤ 0.05), a period also marked by a qualitatively poor diet. The nutritional supplementation prescribed did not fully achieve the reference recommendations, and was poorly complied with by patients. Furthermore, nutritional monitoring was not carried out in all patients, recommended biochemical markers were not screened, and vitamin D depletions occurred. Conclusion: our data suggest that institutions specialized in bariatric patient care may not be adequately adhering to well known guidelines, or applying efficient strategies to improve compliance.

INTRODUCCIÓN: Antecedentes y objetivos: minimizar el deterioro nutricional después del baipás gástrico en Y de Roux (BGYR) puede mejorar los resultados clínicos en el tratamiento de la obesidad. Se evaluaron aspectos nutricionales de mujeres obesas sometidas a BGYR en un hospital universitario de referencia con servicio especializado de cirugía bariátrica. Método: con base en la Ingesta Dietética de Referencia desarrollada por el Consejo de Alimentos y Nutrición del Instituto de Medicina, y las directrices de la Sociedad Estadounidense de Cirugía Bariátrica y Metabólica, evaluamos la adecuación cuantitativa y cualitativa de la ingesta nutricional, la suplementación y el seguimiento bioquímico de 20 mujeres tanto antes como 3 y 12 meses después de un BGYR. Los datos de la ingesta nutricional se obtuvieron mediante la aplicación de diferentes encuestas alimentarias, interpretadas cuantitativamente por el software Virtual Nutri Plus® y utilizando bases de datos nutricionales de referencia. Resultados: se encontraron déficits de ingesta nutricional antes del BGYR (p < 0,05). Estos empeoraron en el postoperatorio (p < 0,05), período también marcado por una mala alimentación cualitativa. La suplementación nutricional prescrita no cumplió plenamente con las recomendaciones de referencia y no fue bien cumplida por los pacientes. Además, la monitorización nutricional no se aplicó en todos los pacientes y no se examinaron todos los marcadores bioquímicos recomendados, hallándose depleciones de vitamina D. Conclusión: nuestros datos sugieren que las instituciones especializadas en la atención de pacientes bariátricos podrían no estar siguiendo adecuadamente las pautas recomendadas, ni aplicando estrategias eficientes para mejorar su cumplimiento.

Distinct pattern of one-carbon metabolism, a nutrient-sensitive pathway, in invasive breast cancer: A metabolomic study.

Altered cell metabolism is a hallmark of cancer and critical for its development. Particularly, activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression. We assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma (IDC). Differences in the metabolic profile between biopsies from IDC (n = 47) and its adjacent tissue (n = 43) and between biopsies from different breast cancer subtypes were assessed by gas spectrometry in targeted (Biocrates Life Science ® ) and untargeted approaches, respectively. The metabolomics data were statistically treated using MetaboAnalyst 4.0, SIMCA P+ (version 12.01), Statistica 10 software and t test with p < 0.05. The Cancer Genome Atlas breast cancer dataset was also assessed to validate the metabolomic profile of IDC. Our targeted metabolomics analysis showed distinct metabolomics profiles between IDC and adjacent tissue, where IDC displayed a comparative enrichment of metabolites involved in one-carbon metabolism (serine, glycine, threonine, and methionine) and a predicted increase in the activity of pathways that receive and donate carbon units (i.e., folate, methionine, and homocysteine). In addition, the targeted and untargeted metabolomics analyses showed similar metabolomics profiles between breast cancer subtypes. The gene set enrichment analysis identified different transcription-related functions between IDC and non-tumor tissues that involved one-carbon metabolism. Our data suggest that one-carbon metabolism may be a central pathway in IDC and even in general breast tumors, representing a potential target for its treatment and prevention.

Fractura de cadera en adultos mayores: Impacto del tratamiento quirúrgico oportuno en la morbimortalidad / Hip Fracture in Elderly Patients: The Impact of Timely Surgical Treatment in Morbimortality

Resumen Introducción Las fracturas de cadera comprenden las regiones de la cabeza, el cuello femoral y la región intertrocantérica. Son una de las causas de morbilidad y mortalidad más importantes en adultos mayores y afectan el equilibrio físico, mental, funcional y social de estos pacientes. Hasta 50% de los pacientes con fractura de cadera, muere en los primeros 6 meses posteriores a la lesión y un gran número de los que sobrevive no recupera su nivel previo de independencia y funcionalidad. La pronta solución quirúrgica disminuye la mortalidad y las complicaciones; cada dos días de espera quirúrgica duplica el riesgo de muerte. Caso clínico Paciente del sexo femenino, de 74 años, que cayó desde su propio plano de sustentación, a consecuencia de lo cual presentó incapacidad para la marcha y dolor progresivo a nivel de cadera derecha. Acudió al servicio de ortopedia para ser valorada 42 días después de la caída. A la exploración física ortopédica: El miembro pélvico derecho en actitud de rotación externa y acortamiento de 1 cm; los arcos de movilidad de cadera, limitados por dolor; la fuerza por grupos musculares no se valoró debido al dolor. Se le realizó radiografía anteroposterior (AP) de pelvis, en la que se observó un trazo simple a nivel subcapital en la cadera derecha. 52 días después de la caída, se le realizó una artroplastia total de cadera derecha. Conclusiones La fractura de cadera es una patología común en pacientes ancianos, y se relaciona con alta morbimortalidad. Es imprescindible un manejo temprano, disminuir el riesgo de complicaciones y la mortalidad.

Abstract Introduction Hip fracture, may occur in the femoral head, neck or in the intertrochanteric line. It is one of the most important causes of morbidity and mortality in elderly patients and it affects the physical, mental, functional and social equilibrium of these patients. Up to 50% of patients with hip fracture die in the first six months after the injury and many those who survive don´t recover their previous level of independence and functionality. Early surgical resolution diminishes mortality and complications. Every two days that the surgery is postponed doubles the risk of death. Case report study A 74-year-old female patient who presented a fall from her own height, is rendered incapable of walking and presents progressive pain in her right hip. She consults an orthopedic doctor for examination 42 days after the fall. Physical examination: right pelvic lower limb with an external rotation and a 1 cm shortness, hip mobility arches limited by pain. Muscle group strength was not examined because of the pain. An AP x-ray of the pelvis was performed that showed a simple trace at subcapital level on the right hip. A total arthroplasty of the right hip was performed 52 days after the patient's fall. Conclusions Hip fracture is a common problem in elderly patients and is associated with a high morbimortality. It is important to handle these cases early to diminish the risk of complications and mortality.

Bladder Dysfunction in an Obese Zucker Rat: The Role of TRPA1 Channels, Oxidative Stress, and Hydrogen Sulfide.

PURPOSE: This study investigates whether functionality and/or expression changes of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels, oxidative stress, and hydrogen sulfide (H2S) are involved in the bladder dysfunction from an insulin-resistant obese Zucker rat (OZR). MATERIALS AND METHODS: Detrusor smooth muscle (DSM) samples from the OZR and their respective controls, a lean Zucker rat (LZR), were processed for immunohistochemistry for studying the expression of TRPA1 and TRPV1 and the H2S synthase cystathionine beta-synthase (CBS) and cysthathionine-γ-lyase (CSE). Isometric force recordings to assess the effects of TRPA1 agonists and antagonists on DSM contractility and measurement of oxidative stress and H2S production were also performed. RESULTS: Neuronal TRPA1 expression was increased in the OZR bladder. Electrical field stimulation- (EFS-) elicited contraction was reduced in the OZR bladder. In both LZR and OZR, TRPA1 activation failed to modify DSM basal tension but enhanced EFS contraction; this response is inhibited by the TRPA1 blockade. In the OZR bladder, reactive oxygen species, malondialdehyde, and protein carbonyl contents were increased and antioxidant enzyme activities (superoxide dismutase, catalase, GR, and GPx) were diminished. CSE expression and CSE-generated H2S production were also reduced in the OZR. Both TRPV1 and CBS expressions were not changed in the OZR. CONCLUSIONS: These results suggest that an increased expression and functionality of TRPA1, an augmented oxidative stress, and a downregulation of the CSE/H2S pathway are involved in the impairment of nerve-evoked DSM contraction from the OZR.

Fractura de cadera: un reto multidisciplinario. Reporte de caso de una víctima del sismo del 19 de septiembre de 2017 / Hip fracture: a multi-disciplinary challenge. Case report from a victim on the September 19, 2017 earthquake

Resumen Introducción La fractura de cadera es la solución de continuidad ósea en la región de la cabeza, cuello o a nivel de trocánter mayor y menor de la cadera. Se estima que 50% de estas afectan el cuello del fémur, 80% se dan en mujeres y estas ocurren principalmente en adultos mayores de 55 años. Es importante recalcar que esta patología tiene un 20-30% de mortalidad dentro del primer año posterior a la lesión, y que más del 50% será incapaz de reincorporarse a sus actividades de la vida cotidiana1. La mayoría de los pacientes que la padecen presenta una patología sistémica asociada (siendo las más frecuentes enfermedades cardiovasculares, enfermedades respiratorias, diabetes mellitus, déficit sensoriales o neurológicos, problemas de movilidad o equilibrio, desnutrición y demencia). Presentación del caso clínico Mujer de 22 años con antecedente de DM Tipo I diagnosticada a los 10 años, tuberculosis pulmonar diagnosticada en diciembre de 2016 en tratamiento y desnutrición; quien sufrió caída de su propia altura e inició con dolor y limitación del movimiento de la pierna del lado derecho. A la exploración física dirigida: miembro pélvico derecho con arcos de movilidad de cadera limitados con dolor a nivel de trocánter mayor, presencia de acortamiento clínico de aproximadamente 2 cm y en rotación externa. Se le realizó radiografía AP de pelvis donde se observó un trazo simple a nivel transtrocantérico y fragmentación del trocánter menor. Se le realizó reducción cerrada fijación interna con PBM de tutor, más protección con clavo centromedular para fémur proximal PF 110 × 75 y se interconsulta al servicio de medicina interna, psiquiatría, nutrición y rehabilitación del hospital. Conclusiones Las fracturas de cadera son una patología con un elevado índice de morbimortalidad en un periodo de un año posterior a la lesión. Requieren un abordaje quirúrgico inmediato y un enfoque multidisciplinario para disminuir esta incidencia. El objetivo tras el tratamiento es conseguir el nivel de independencia y de deambulación previos.

Abstract Introduction The hip fracture is the bone continuity solution in the head, neck or at the level of the greater and lesser trochanter of the hip. Aproximately, 50% of the fractures affect the neck of the femur, 80% occur in women and they occur mainly in adults over 55 years old. It's important to emphasize that this pathology has a 20-30% mortality within the first year after the injury and more than 50% will be unable to rejoin their daily activities1. The majority of patients who suffer from it have an associated systemic pathology (the most frequent being cardiovascular diseases, respiratory diseases, diabetes mellitus, sensory or neurological deficits, mobility or balance problems, malnutrition and dementia). Case report study 22-year-old female with a history of DM Type I diagnosed at age 10, in treatment for a pulmonary tuberculosis diagnosed in December of 2016, and malnutrition. She suffered a fall, starting with pain and limited movement in the leg on the right side. On the directed physical examination: right pelvic member with limited hip arc movement with pain at the level of greater trochanter, presenting clinical shortening of approximately 2 cm and in external rotation of the leg. An AP pelvis radiography was performed where a simple trace at the transtrochanteric level and fragmentation of the lesser trochanter was observed. A closed reduction with internal fixation with an intramedullary nail for proximal femur PF 110 × 75 was performed and was channeled to interconsultation to the departments of internal medicine, psychiatry, nutrition and rehabilitation of the hospital. Conclusions Hip fractures are a pathology with a high rate of morbidity and mortality in a period of one year after the injury. They require an immediate surgical solution and a multidisciplinary approach to reduce the incidence of complications. The objective after the treatment is to achieve the same amount of independence and ambulation as before the injury.

Role of endogenous hydrogen sulfide in nerve-evoked relaxation of pig terminal bronchioles.

Hydrogen sulfide (H2S) is a gasotransmitter employed for intra- and inter-cellular communication in almost all organ systems. This study investigates the role of endogenous H2S in nerve-evoked relaxation of pig terminal bronchioles with 260 µm medium internal lumen diameter. High expression of the H2S synthesis enzyme cystathionine γ-lyase (CSE) in the bronchiolar muscle layer and strong CSE-immunoreactivity within nerve fibers distributed along smooth muscle bundles were observed. Further, endogenous H2S generated in bronchiolar membranes was reduced by CSE inhibition. In contrast, cystathionine ß-synthase expression, another H2S synthesis enzyme, however was not consistently detected in the bronchiolar smooth muscle layer. Electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked smooth muscle relaxation. Inhibition of CSE, nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and of ATP-dependent K+, transient receptor potential A1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels reduced the EFS relaxation but failed to modify the GYY4137 response. Raising extracellular K+ concentration inhibited the GYY4137 relaxation. Large conductance Ca2+-activated K+ channel blockade reduced both EFS and GYY4137 responses. GYY4137 inhibited the contractions induced by histamine and reduced to a lesser extent the histamine-induced increases in intracellular [Ca2+]. These results suggest that relaxation induced by EFS in the pig terminal bronchioles partly involves the H2S/CSE pathway. H2S response is produced via NO/sGC-independent mechanisms involving K+ channels and intracellular Ca2+ desensitization-dependent pathways. Thus, based on our current results H2S donors might be useful as bronchodilator agents for the treatment of lung diseases with persistent airflow limitation, such as asthma and chronic obstructive lung disease.

Underlying mechanisms involved in progesterone-induced relaxation to the pig bladder neck.

Progesterone increases bladder capacity and improves the bladder compliance by its relaxant action on the detrusor. A poor information, however, exists concerning to the role of this steroid hormone on the bladder outflow region contractility. This study investigates the progesterone-induced action on the smooth muscle tension of the pig bladder neck. To this aim, urothelium-denuded bladder neck strips were mounted in myographs for isometric force recordings and for simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)]i) and tension. On phenylephrine (PhE)-precontracted strips, progesterone produced concentration-dependent relaxations only at high pharmacological concentrations. The blockade of progesterone receptors, nitric oxide (NO) synthase, guanylyl cyclase, large conductance Ca(2+)-activated K(+) (BKCa) or ATP-dependent K(+) (KATP) channels reduced the progesterone relaxations. The presence of the urothelium and the inhibition of cyclooxygenase (COX), intermediate- and small-conductance Ca(2+)-activated K(+) channels failed to modify these responses. In Ca(2+)-free potassium rich physiological saline solution, progesterone inhibited the contraction to CaCl2 and to the L-type voltage-operated Ca(2+) (VOC) channel activator BAY-K 8644. Relaxation induced by progesterone was accompanied by simultaneous decreases in smooth muscle [Ca(2+)]i. These results suggest that progesterone promotes relaxation of pig bladder neck through smooth muscle progesterone receptors via cGMP/NO pathway and involving the activation of BKCa and KATP channels and inhibition of the extracellular Ca(2+) entry through L-type VOC channels.

Hydrogen sulfide mediated inhibitory neurotransmission to the pig bladder neck: role of KATP channels, sensory nerves and calcium signaling.

PURPOSE: Because neuronal released endogenous H2S has a key role in relaxation of the bladder outflow region, we investigated the mechanisms involved in H2S dependent inhibitory neurotransmission to the pig bladder neck. MATERIALS AND METHODS: Bladder neck strips were mounted in myographs for isometric force recording and simultaneous measurement of intracellular Ca(2+) and tension. RESULTS: On phenylephrine contracted preparations electrical field stimulation and the H2S donor GYY4137 evoked frequency and concentration dependent relaxation, which was reduced by desensitizing capsaicin sensitive primary afferents with capsaicin, and the blockade of adenosine 5'-triphosphate dependent K(+) channels, cyclooxygenase and cyclooxygenase-1 with glibenclamide, indomethacin and SC560, respectively. Inhibition of vanilloid, transient receptor potential A1, transient receptor potential vanilloid 1, vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide and calcitonin gene-related peptide receptors with capsazepine, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively, also decreased electrical field stimulation and GYY4137 responses. H2S relaxation was not changed by guanylyl cyclase, protein kinase A, or Ca(2+) activated or voltage gated K(+) channel inhibitors. GYY4137 inhibited the contractions induced by phenylephrine and by K(+) enriched (80 mM) physiological saline solution. To a lesser extent it decreased the phenylephrine and K(+) induced increases in intracellular Ca(2+). CONCLUSIONS: H2S produces pig bladder neck relaxation via activation of adenosine 5'-triphosphate dependent K(+) channel and by smooth muscle intracellular Ca(2+) desensitization dependent mechanisms. H2S also promotes the release of sensory neuropeptides and cyclooxygenase-1 pathway derived prostanoids from capsaicin sensitive primary afferents via transient receptor potential A1, transient receptor potential vanilloid 1 and/or related ion channel activation.

Claudin-6, 7, or 9 overexpression in the human gastric adenocarcinoma cell line AGS increases its invasiveness, migration, and proliferation rate.

Altered claudin expression is related to metastatic potential, poor prognosis, or tumor recurrence. We analyzed if the overexpression of claudin-6, claudin-7, or claudin-9 in AGS cells altered cell motility, invasiveness, or proliferation rate. Claudin-7, claudin-9, and claudin-6 enhanced their invasive potential by 3.4-fold, 1.6-fold, and 2.0-fold, respectively. Claudin-6 and claudin-9 enhanced cell migration, while the proliferation rate of claudin-6-, claudin-7-, and claudin-9-transfected cells increased by 12.7%, 9.0%, and 13.3%, respectively. Claudin-7 and claudin-9 overexpression increased claudin-1 and zonula occludens-1 levels. In summary, individual increased expression of claudin-6, claudin-7, or claudin-9 is sufficient to enhance tumorigenic properties of a gastric adenocarcinoma cell line.

Regulation of NO-dependent acetylcholine relaxation by K+ channels and the Na+-K+ ATPase pump in porcine internal mammary artery.

This study was designed to determine whether K+ channels play a role in nitric oxide (NO)-dependent acetylcholine relaxation in porcine internal mammary artery (IMA). IMA segments were isolated and mounted in organ baths to record isometric tension. Acetylcholine-elicited vasodilation was abolished by muscarinic receptor blockade with atropine (10(-6)M). Incubation with indomethacin (3 x 10(-6)M), superoxide dismutase (150 U/ml) and bosentan (10(-5)M) did not modify the acetylcholine response ruling out the participation of cyclooxygenase-derivates, reactive oxygen species or endothelin. The relaxation response to acetylcholine was strongly diminished by NO synthase- or soluble guanylyl cyclase-inhibition using L-NOArg (10(-4)M) or ODQ (3 x 10(-6)M), respectively. The vasodilation induced by acetylcholine and a NO donor (NaNO(2)) was reduced when rings were contracted with an enriched K+ solution (30 mM), by voltage-dependent K+ (K(v)) channel blockade with 4-amynopiridine (4-AP; 10(-4)M), by Ca(2+)-activated K+ (K(Ca)) channel blockade with tetraethylammonium (TEA; 10(-3)M), and by apamin (5 x 10(-7)M) plus charybdotoxin (ChTx; 10(-7)M) but not when these were added alone. In contrast, large conductance K(Ca) (BK(Ca)), ATP-sensitive K+ (K(ATP)) and inwardly rectifying K+ (K(ir)) channel blockade with iberiotoxin (IbTx; 10(-7)M), glibenclamide (10(-6)M) and BaCl(2) (3 x 10(-5)M), respectively, did not alter the concentration-response curves to acetylcholine and NaNO(2). Na+-K+ ATPase pump inhibition with ouabain (10(-5)M) practically abolished acetylcholine and NaNO(2) relaxations. Our findings suggest that acetylcholine-induced relaxation is largely mediated through the NO-cGMP pathway, involving apamin plus ChTx-sensitive K+ and K(v) channels, and Na+-K+-ATPase pump activation.

5-hydroxytryptamine induced relaxation in the pig urinary bladder neck.

BACKGROUND AND PURPOSE: 5-Hydroxytryptamine (5-HT) is one of the inhibitory mediators in the urinary bladder outlet region. Here we investigated mechanisms involved in 5-HT-induced relaxations of the pig bladder neck. EXPERIMENTAL APPROACH: Urothelium-denuded strips of pig bladder were mounted in organ baths for isometric force recordings of responses to 5-HT and electrical field stimulation (EFS). KEY RESULTS: After phenylephrine-induced contraction, 5-HT and 5-HT receptor agonists concentration-dependently relaxed the preparations, with the potency order: 5-carboxamidotryptamine (5-CT) > 5-HT = RS67333 > (+/-)-8-hydroxy-2-dipropylaminotetralinhydrobromide > m-chlorophenylbiguanide > alpha-methyl-5-HT > ergotamine. 5-HT and 5-CT relaxations were reduced by the 5-HT(7) receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulphonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride and potentiated by (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide dihydrochloride (WAY 100135) and cyanopindolol, 5-HT(1A) and 5-HT(1A/1B) receptor antagonists respectively. Inhibitors of 5-HT(1B/1D), 5-HT(2), 5-HT(2B/2C), 5-HT(3), 5-HT(4), 5-HT(5A) and 5-HT(6) receptors failed to modify 5-HT responses. Blockade of monoamine oxidase A/B, noradrenergic neurotransmission, alpha-adrenoceptors, muscarinic and purinergic receptors, nitric oxide synthase, guanylate cyclase and prostanoid synthesis did not alter relaxations to 5-HT. Inhibitors of Ca(2+)-activated K(+) and ATP-dependent K(+) channels failed to modify 5-HT responses but blockade of neuronal voltage-gated Na(+)-, Ca(2+)- and voltage-gated K(+) (K(v))-channels potentiated these relaxations. Adenylyl cyclase activation and cAMP-dependent protein kinase (PKA) inhibition potentiated and reduced, respectively, 5-HT-induced responses. Under non-adrenergic, non-cholinergic, non-nitrergic conditions, EFS induced neurogenic, frequency-dependent, relaxations which were resistant to WAY 100135 and cyanopindolol. CONCLUSIONS AND IMPLICATIONS: 5-HT relaxed the pig urinary bladder neck through muscle 5-HT(7) receptors linked to the cAMP-PKA pathway. Prejunctional 5-HT(1A) receptors and K(v) channels modulated 5-HT-induced relaxations whereas postjunctional K(+) channels were not involved in such responses. 5-HT(7) receptor antagonists could be useful in the therapy of urinary incontinence produced by intrinsic sphincter deficiency.

Plasma levels and vascular effects of vasopressin in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Recent studies have suggested that endogenous vasopressin (AVP) acts as a spasmogen during coronary artery bypass grafting (CABG). Given that AVP could induce vasospasm in the grafted vessel, we assessed the release of this peptide during and after CABG, and explored ways of counteracting its contractile effect on the internal mammary artery (IMA). METHODS: Plasma levels of AVP were determined by radioimmunoassay in 16 patients before, during and after CABG. Using isometric force recording techniques, we also investigated the mechanisms involved in the contractile effect of AVP in ring preparations of IMA specimens taken from 95 patients. RESULTS: Plasma AVP levels peaked after the start of cardiopulmonary bypass (CPB) and correlated well with serum osmolality (Pearson's r=0.9490; P<0.0001; n=16). An inverse correlation was observed between plasma AVP levels recorded at this stage and the maximal contraction induced in vitro by AVP in vascular rings from the same patients (Pearson's r=-0.6968; P<0.01; n=16). No change in the AVP response was produced by endothelium removal, exposure to the NO precursor (3 x 10(-4)M L-arginine), inhibition of nitric oxide (NO) synthase (3 x 10(-5) M L-NAME) or soluble guanylate cyclase (3 x 10(-6) M 1H-[1,2,4]oxadiazol [4,3,-alpha]quinoxalin-1-one (ODQ)), removal of the superoxide anion (100 U/ml superoxide dismutase (SOD) plus 1200 U/ml catalase) or hydroxyl radical (10(-4) M deferoxamine), or specific alpha1 - (10(-6) M prazosin) or endothelin (10(-5) M bosentan) receptor antagonism. In contrast, adenylate cyclase activation (3 x 10(-8) M forskolin) reduced the contractile response to AVP, while prostanoid synthesis (3 x 10(-6) M indomethacin) inhibition and blockade of Ca2+ -activated potassium channels (KCa) (10(-3) M tetraethylammonium (TEA)) enhanced AVP contraction. Age, gender and smoking also modified the AVP response. CONCLUSION: Our findings suggest a role for AVP as a modulator of vascular tone in human IMA. The effect of AVP is dependent on prostanoids and Ca2+ -activated K+ channels, so its dysfunction in pathophysiological cardiovascular processes could mean that AVP, among other factors, produces vasospasm in IMA grafts.

Complicaciones en las fracturas complejas de la meseta tibial y factores asociados / Complications in complex fractures of the tibial plateau and associated factors

Objetivo: identificar factores asociados a complicaciones con el manejo quirúrgico de las fracturas complejas de la meseta tibial. Material y métodos: estudio de casos y controles. Muestra integrada con expedientes de 56 pacientes diagnosticados con fractura compleja de la meseta tibial (tipos IV, V y VI de Schatzker), tiempo de seguimiento promedio de 12.9 ± 3.2 meses (8 a 18), y con uno o más de los siguientes factores de riesgo: edad mayor de 50 años, comorbilidad, tiempo de isquemia mayor de 60 minutos y fractura tipo IV, V o VI. Se consideró caso al paciente que presentara una o más complicaciones. Resultados: la edad promedio fue de 50.1 ± 15.7 años (17 a 87); 35 pacientes (62.5 %) pertenecieron al sexo masculino. Los pacientes con o sin complicaciones mostraron homogeneidad respecto a edad, sexo, lado, tipo de fractura y tiempo de seguimiento; 41.1 % presentó antecedentes patológicos. En todos los procedimientos se utilizó torniquete neumático. El tiempo promedio de cirugía fue de 91 ± 27.2 minutos (40 a 175). Los tratamientos empleados fueron placa más tornillos (53.6 %), fijadores externos más tornillos (35.7 %), doble placa y clavo centromedular. 37.5 % desarrolló complicaciones: infección superficial, 16.1 %; deformidades angulares residuales, 10.7 % (varo, 7.1 %); lesión del nervio peroneo, 5.4 %, pseudoartrosis, 3.5 %; trombosis venosa profunda, 1.8 %. Presentó más de una complicación, 22.2 %. Conclusiones: los factores de riesgo asociados significativamente a complicaciones con el manejo de la fractura compleja de la meseta tibial, fueron la edad mayor de 60 años y el tiempo de isquemia transoperatoria mayor de 120 minutos. Los pacientes en estas condiciones presentaron tres veces más riesgo para desarrollar complicaciones.

BACKGROUND: We undertook this study to identify factors associated with surgical complications of complex fractures of the tibial plateau. METHODS: We designed a case-control study with 56 patients with a diagnosis of complex fracture in the tibial plateau (IV-VI Schatzker) and with 12.9 +/- 3.2 (8-18) months of follow-up. Risk factor exposure was defined as having one or more of the following characteristics: age >60 years; co-morbidity (diabetes mellitus, systemic arterial hypertension); time of [quot ]Kidde[quot ] (>60, >90, >120 min) and fracture type IV, V or VI. A case was considered with one or more complications. Results: Mean age was 50.1 +/- 15.7 (17-87) years old; 35 patients (62.5%) were males. Homogeneity between groups was shown for age, sex, side effects, type of fracture and time of follow-up; 41.1% of patients had pathological history. All surgeries used pneumatic compression (Kidde) for 91 +/- 27.2 (40-175) min. The implants used were plate plus cancellous screws (53.6%), external fixators plus cancellous screws (35.7%), double plate and intramedullary nail. Complications appeared in 37.5% of all patients. Complications reported were superficial infection (16.1%), residual angular deformities (10.7%, varum [7.1%]), peroneal nerve injury (5.4%), non-union (3.5%) and deep venous thrombosis (1.8%); 22.2% of all patients presented more than one complication. CONCLUSIONS: Statistically significant risk factors were age >60 years and pneumatic compression >120 min. Patients with one of these characteristics had a three-times risk of complications. No association was demonstrated between type of fracture, surgical treatment, time between injury and the surgery, with development of complications.

Blunted non-nitric oxide vasodilatory neurotransmission in penile arteries from renal hypertensive rats.

The present study was designed to explore whether there are any effects on neurogenic responses in penile small arteries during the development of hypertension in a one-kidney, one-clip (1K1C) model, a non-renin-dependent model of renovascular hypertension. Five weeks after surgery, male Sprague-Dawley rats were given vehicle, bendroflumethiazide (7.5 mg/kg/day), or L-arginine (2 g/kg/day) in their drinking water for five weeks. Experiments were performed on penile small artery rings (150-200 microm) mounted on microvascular myographs for electrical field stimulation (EFS), and erectile tissue was processed for immunohistochemistry. Maximal neurogenic contractions were unmodified in penile preparations. Relaxations induced by EFS were reduced in the presence of ADMA. In 1K1C rats, neurogenic vasorelaxation mediated by nitric oxide (NO) was unaltered, while relaxation resistant to NO synthase inhibition was blunted. L-arginine and bendroflumethiazide lowered blood pressure in 1K1C rats, but vasodilation was still blunted in the penile arteries. Immunoreactivity for factor VIII and neuronal NO synthase was unaltered in penile arteries from 1K1C animals. Endothelium-dependent vasorelaxation evoked by acetylcholine was also blunted in preparations from 1K1C rats, while exogenous NO relaxation was unaffected. Plasma concentrations and urinary excretion of ADMA did not differ among the experimental animals. Our findings indicate that the reduced release of a non-NO vasodilatory neurotransmitter accounts for the impaired neurogenic vasodilation of the penile arteries. Although ADMA inhibits penile vasorelaxation, it is unlikely to affect erectile function in 1K1C rats.

[Complications in complex fractures of the tibial plateau and associated factors]. / Complicaciones en las fracturas complejas de la meseta tibial y factores asociados.

BACKGROUND: We undertook this study to identify factors associated with surgical complications of complex fractures of the tibial plateau. METHODS: We designed a case-control study with 56 patients with a diagnosis of complex fracture in the tibial plateau (IV-VI Schatzker) and with 12.9 +/- 3.2 (8-18) months of follow-up. Risk factor exposure was defined as having one or more of the following characteristics: age >60 years; co-morbidity (diabetes mellitus, systemic arterial hypertension); time of "Kidde" (>60, >90, >120 min) and fracture type IV, V or VI. A case was considered with one or more complications. RESULTS: Mean age was 50.1 +/- 15.7 (17-87) years old; 35 patients (62.5%) were males. Homogeneity between groups was shown for age, sex, side effects, type of fracture and time of follow-up; 41.1% of patients had pathological history. All surgeries used pneumatic compression (Kidde) for 91 +/- 27.2 (40-175) min. The implants used were plate plus cancellous screws (53.6%), external fixators plus cancellous screws (35.7%), double plate and intramedullary nail. Complications appeared in 37.5% of all patients. Complications reported were superficial infection (16.1%), residual angular deformities (10.7%, varum [7.1%]), peroneal nerve injury (5.4%), non-union (3.5%) and deep venous thrombosis (1.8%); 22.2% of all patients presented more than one complication. CONCLUSIONS: Statistically significant risk factors were age >60 years and pneumatic compression >120 min. Patients with one of these characteristics had a three-times risk of complications. No association was demonstrated between type of fracture, surgical treatment, time between injury and the surgery, with development of complications.

Endothelial mechanisms underlying responses to acetylcholine in the horse deep dorsal penile vein.

This study evaluates the mechanisms underlying endothelium-dependent responses to acetylcholine in horse deep dorsal penile veins. Acetylcholine-induced relaxation was abolished by endothelium removal, the soluble guanylyl cyclase-inhibitor, and the nitric oxide (NO) synthase inhibitors. Acetylcholine-induced relaxation was inhibited by high K+ concentrations and blockade of large-conductance Ca(2+)-activated potassium (BK(Ca)) channels, and voltage-dependent potassium (K(v)) channels. Relaxations were unaffected by a small-conductance K(Ca) (SK(Ca)) channel blocker, or an ATP-sensitive potassium (K(ATP)) channel blocker. Relaxation in response to a NO donor was unaffected by K(Ca) channel blockers, but inhibited by high K+ concentrations and a K(v) channel blocker. In the presence of a NO synthase inhibitor, acetylcholine-induced contractions were inhibited by a cyclooxygenase blocker and abolished by endothelial removal. The contractile response was competitively inhibited by muscarinic receptor antagonists, high affinity M1 and M3 antagonists, while the M2 antagonist had no effect. The pharmacological profile suggests that acetylcholine contraction is mediated by muscarinic M1 receptors. Our findings indicate that acetylcholine-induced relaxation in the horse deep dorsal penile vein is essentially mediated by NO, acting via the cGMP-dependent pathway and opening of K+ channels. The contraction elicited by acetylcholine is prostanoid-mediated and induced by endothelial muscarinic M1 receptor activation.

Heterogeneity of neuronal and smooth muscle receptors involved in the VIP- and PACAP-induced relaxations of the pig intravesical ureter.

1. The mechanisms and receptors involved in the vasoactive intestinal peptide (VIP)- and pituitary adenylate cyclase-activating polypeptide (PACAP)-induced relaxations of the pig intravesical ureter were investigated. 2. VIP, PACAP 38 and PACAP 27 concentration-dependently relaxed U46619-contracted ureteral strips with a similar potency. [Ala(11,22,28)]-VIP, a VPAC(1) agonist, showed inconsistent relaxations. 3. The neuronal voltage-gated Ca(2+) channel inhibitor, omega-conotoxin GVIA (omega-CgTX, 1 microm), reduced the VIP relaxations. Urothelium removal or blockade of capsaicin-sensitive primary afferents, nitric oxide (NO) synthase and guanylate cyclase with capsaicin (10 microm), N(G)-nitro-l-arginine (l-NOARG, 100 microm) and 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 microm), respectively, did not change the VIP relaxations. However, the PACAP 38 relaxations were reduced by omega-CgTX, capsaicin, l-NOARG and ODQ. 4. The VIP and VIP/PACAP receptor antagonists, [Lys(1), Pro(2,5), Arg(3,4), Tyr(6)]-VIP (1 microm) and PACAP (6-38) (0.4 microm), inhibited VIP and VIP and PACAP 38, respectively, relaxations. 5. The nonselective and large-conductance Ca(2)-activated K(+) channel blockers, tetraethylammonium (3 mm) and charybdotoxin (0.1 microm), respectively, and neuropeptide Y (0.1 microm) did not modify the VIP relaxations. The small-conductance Ca(2)-activated K(+) channel blocker apamin (1 microm) did not change the PACAP 27 relaxations. 6. The cAMP-dependent protein kinase A (PKA) blocker, 8-(4-chlorophenylthio)adenosine-3',5'-cyclic monophosphorothioate (Rp-8-CPT-cAMPS, 100 microm), reduced VIP relaxations. The phosphodiesterase 4 inhibitor rolipram and the adenylate cyclase activator forskolin relaxed ureteral preparations. The rolipram relaxations were reduced by Rp-8-CPT-cAMPS. Forskolin (30 nm) evoked a potentiation of VIP relaxations. 7. These results suggest that VIP and PACAP relax the pig ureter through smooth muscle receptors, probably of the VPAC(2) subtype, linked to a cAMP-PKA pathway. Neuronal VPAC receptors localized at motor nerves and PAC(1) receptors placed at sensory nerves and coupled to NO release, seem also to be involved in the VIP and PACAP 38 relaxations.

Epidemiología, un gran apoyo a la gerencia hospitalaria / Epidemiology, a great support to the hospital managing

El crecimiento demográfico mundial ha provocado una desproporción entre recursos y necesidades. El aumento de la población a mayor velocidad que la producción de bienes y la eclosión demográfica actual han originado un cambio sustancial en forma de vida de los individuos y una transformación epidemiológica importante con cambios marcados en la incidencia de algunas enfermedades y la aparición de otras...