Controversial alkoxyl and peroxyl radical scavenging activity of the tryptophan metabolite 3-hydroxy-anthranilic acid.

3-Hydroxy-anthranilic acid (3-OHAA), a tryptophan metabolite produced in the kynurenine pathway, is an efficient antioxidant towards peroxyl radicals (ROO) derived from the AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride) thermolysis. However, self-reactions of ROO can give rise to alkoxyl radicals (RO), which could strongly affect the fate of scavenging reactions. In the present work, we studied the influence of RO in the scavenging activity of 3-OHAA in three different systems: i) Monitoring of the direct reaction between 3-OHAA and AAPH-derived free radicals (kinetic studies); ii) Evaluation of the protective effect of 3-OHAA on the AAPH-induced consumption of fluorescein; and, iii) Inhibition, given by 3-OHAA, of the AAPH-initiated lipid peroxidation of both, rat brain synaptosomes and homogenate preparations (assessed by chemiluminescence). For such purposes, the fraction of free radicals (f) trapped per 3-OHAA molecule was determined in each system. Kinetic results show that the oxidation of 3-OHAA follows a process dominated by ROO with a zero order kinetic limit in 3-OHAA, and a fraction (fri) equal to 0.88. From the induction times, elicited by 3-OHAA in the kinetic profiles of fluorescein consumption, a fraction (fT) of 0.28 was determined. 3-OHAA also generated induction times in the kinetic profiles of light emission during the AAPH-initiated lipid peroxidation of rat brain synaptosomes and homogenates. From such induction times, fractions of 0.61 and 0.63 were determined for rat brain synaptosomes (fsyn) and homogenates (fhom), respectively. These results show that during the incubation of 3-OHAA and AAPH, a low fraction of ROO self-reacts to generate RO. Nevertheless, when 3-OHAA is employed to protect particular targets, such as fluorescein, rat brain synaptosomes and homogenates, reactions of ROO and/or RO should be considered.

Reaction of tetracycline with biologically relevant chloramines.

Helicobacter pylori (H. pylori) infection triggers inflammatory processes with the consequent production of hypochlorous acid (HOCl), monochloramine (NH2Cl), and protein-derived chloramines. As the therapy for eradicating H. pylori is partially based on the use of tetracycline, we studied the kinetic of its consumption elicited by HOCl, NH2Cl, N-chloro-n-butylamine (NHCl-But, used as a lysine-derived chloramine model), and lysozyme-derived chloramines. In the micromolar concentration range, tetracycline reacted rapidly with HOCl, generating in the first few seconds intermediates of short half-life. In contrast, a slow tetracycline consumption was observed in the presence of high NH2Cl and NHCl-But concentrations (millimolar range). Similar chlorinated products of tetracycline were identified by mass spectrometry, in the presence of HOCl and NH2Cl. These results evidenced that tautomers of tetracycline are pivotal intermediates in all reactions. In spite of the low reactivity of chloramines towards tetracycline, it is evident that, in the concentration range where they are produced in a H. pylori infection (millimolar range), the reactions lead to oxidation and/or chlorination of tetracycline. This kind of reactions, which were also observed triggered by lysozyme-derived chloramines, could limit the efficiency of the tetracycline-based therapy.

First evidence of pre-Hispanic dentistry in South America - Insights from Cusco, Peru.

Intentional dental modification (IDM) derived from archeological or ethnographic contexts has been extensively documented across the globe. Despite the wealth of information on IDM for personal ornamentation and ritualistic purposes, evidence of IDM for therapeutic reasons among early Native Americans is poorly known and limited to a handful of cases. We report two upper canines from two pre-Hispanic individuals dated to the Late Horizon Period from Cusco (Peru), each showing a conical perforation on its incisal surface. Analyses were performed using traditional radiography, computed tomography and scanning electron microscopy. The depth and symmetrical location of the perforations at the center of the crown suggest that these two teeth were artificially drilled, rather than affected by taphonomic factors. The poor oral health of the individuals, the location of the perforations on the incisal surface, and evidence of intentional manipulation of the pulp chambers (as supported by their overall morphology and presence of striations and deep marks along the walls of the perforations) provide a strong case for the occurrence of prehistoric dentistry in the New World. The two canine teeth reported here represent the first pre-Columbian examples of IDM likely performed to ameliorate a dental pathology (presumably associated with the infection of the dental pulp) found in Peru and in the rest of South America.

Experiencia clínica en segundos cánceres primarios / Second primary cancer: review of 196 cases

Background: A second primary cancer is that occurring in patients who have survived a previous cancer and its frequency is 16 percent. Aim: To identify and characterize patients with a second primary cancer treated in a clinical hospital. Material and methods: Review of the database of the Clinical Oncology Unit of a surgical department between 2004 and 2012. Among 4,007 patients operated for cancer, 196 (mean age 63 years, 51 percent women) had a previous history of cancer, whose medical records were reviewed. Results: In the study period the frequency of a second primary cancer in endocrinological, thoracic and digestive surgery was 4.9 percent. There was a mean lapse of 8.2 years between the first and second cancer and 24 percent of patients had a family history of cancer. The second primary lesions were located in colon in 26 percent, stomach in 19 percent, thyroid in 16 percent, rectum in 12 percent, pancreas in 8 percent and lung in 8 percent. Sixty five percent of lesions was diagnosed in stage IV with peritoneal and lung metastases in 38 and 25 percent respectively. Conclusions: Second primary cancer is uncommon in this series. The high frequency of colon cancer must be highlighted. Due to the lapse between the first and second tumor, follow up of patients treated for cancer should be maintained for at least eight years.

Introducción: El segundo cáncer primario (SCP) es aquel ocurrido en pacientes sobrevivientes de cáncer y tiene una frecuencia de 16 por ciento según Surveillance Epidemiology and End Results. Objetivo: Identificar y caracterizar a los pacientes con SCP en nuestro hospital entre los años 2004 y 2012. Materiales y métodos: Estudio observacional descriptivo retrospectivo. Revisión en base de datos registrados en la Unidad de Oncología Clínica del Departamento de Cirugía entre 2004-2012. De un total de 4.007 pacientes operados por cáncer, se identificaron 196 con antecedentes previos de cáncer. Revisión de fichas Clínicas, Registro en programa Excel y análisis en sistema Stata v11. Resultados: El SCP en cirugía endocrinológica, torácica, coloproctológica y digestiva tiene una frecuencia de 4,9 por ciento en el período estudiado. La edad promedio de presentación es 63 años, 51 por ciento mujeres y 48 por ciento varones. Intervalo promedio de 8,2 años entre el primer y el segundo cáncer. 23,47 por ciento tenía antecedentes familiares. Los pacientes presentaron cáncer de colon en un 26,02 por ciento, seguido de cáncer gástrico 18,88 por ciento, cáncer de tiroides 15,8 por ciento, cáncer de recto 11,73 por ciento, cáncer de páncreas 8,16 por ciento, cáncer de pulmón 7,65 por ciento. El 65,5 por ciento fue diagnosticado en etapa IV, siendo las metástasis más frecuentes al peritoneo (37,5 por ciento) y pulmón (25 por ciento). Conclusión: El segundo primario es una entidad poco frecuente en nuestro medio, destacando la alta incidencia de cáncer de colon. El intervalo de presentación sugiere mantener un seguimiento prolongado de al menos 8 años.

Electrical stimulation device as possible treatment for nocturnal bruxism: preliminary results.

Nocturnal bruxism (NB) is a temporomandibular disorder characterized by an excessive clenching and involuntary parafunctional grinding of the teeth during sleep. It can cause dental damage and irreversible temporomandibular joint dysfunction. We designed a device that generates electrical stimulation on inhibitory sensory afferents when an EMG signal is measured. This stimulation was applied to the right mental nerve to produce a decrease in the contraction intensity of the mandibular elevation muscles. To measure the intensity of contraction, electromyographic (EMG) signal of the left temporalis anterior (LTa) muscle was used. The results showed that, on average, the percentage decrease in the bruxist group was 30.53% and for the control group was 28.91%. These results indicate that the device implemented generates an important decrease in the muscle contractile activity. Therefore, the device could be useful as a possible treatment to decrease nocturnal bruxism.

Effects of ionizing radiation and preservation on biomechanical properties of human costal cartilage.

Tissue banks around the world store human cartilage obtained from cadaveric donors for use in diverse reconstructive surgical procedures. To ensure this tissue is sterile at the time of distribution, tissues may be sterilized by ionizing radiation. In this work, we evaluate the physical changes in deep frozen costal cartilage (-70 °C) or costal cartilage preserved in high concentrations of glycerol (>98 %) followed by a terminal sterilization process using ionizing radiation, at 3 different doses (15, 25 and 50 kGy). Tension and compression tests were carried out to determine the mechanical changes related both to the different preservation methods and irradiation doses. For both methods of preservation, tension strength was increased by about 24 %, when cartilage tissue was irradiated with 15 kGy. Deep frozen samples, when irradiated with 25 or 50 kGy, had a decrease in their mechanical performance, albeit to a lesser extent than when tissues were preserved in high concentration of glycerol and equally irradiated. In conclusion, processing in high concentration of glycerol did not increase tissue protection against radiation damage; while cartilage preserved in high concentrations of glycerol withstands radiation up to 25 kGy, deep frozen human costal cartilage may be sterilized with a doses up to 50 kGy without significant mechanical impact.

On the occurrence of Anaecypris hispanica, an extremely endangered Iberian endemism, in the Guadalquivir River basin.

The jarabugo Anaecypris hispanica, considered endemic to the Guadiana River basin, has been found in the Guadalquivir River. First genetic data showed a high degree of similarity to those of the Guadiana River populations. The genetic study recovered five different groups of haplotypes, the Guadalquivir River specimens belong to the largest and most widely extended group.

Antioxidant properties of alpha-crystallin.

alpha-Crystallin is a major chaperone lens protein to which has been ascribed antioxidant functions. In the present work we have evaluated the antioxidant and free radical scavenging properties of bovine alpha-crystallin in a series of in vitro models: zimosan-induced, luminol-enhanced chemiluminescence response of polymorphonuclear leukocytes, the autoxidation of brain homogenate, bleaching of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)-derived radical cations, trapping of peroxyl radicals, and reactivity toward hypochloric acid. In all these systems, the reactivity of alpha-crystallin is higher than or similar to that of bovine serum albumin. It is concluded that, given the high concentrations of ol-crystallin in the lenses, its capacity to interact with free radicals and to remove hypochlorous acid could contribute to the maintenance of the lens functionality.

Singlet oxygen-mediated photobleaching of the prosthetic group in hemoglobins and c-phycocyanin.

Proteins bearing colored prosthetic groups, such as the heme group in hemoglobin or the bilin group in c-phycocyanin, quench singlet oxygen by interactions at the apoprotein and the prosthetic group levels. In both proteins, chemical modification of the chromophore constitutes only a minor reaction pathway. While total deactivation of singlet oxygen takes place with rate constants of 4.0 x 10(9) and 4.2 x 10(8) M-1 s-1 for hemoglobin and phycocyanin, respectively, the bleaching of the chromophore takes place with rate constants of 3.2 x 10(6) and approximately 1 x 10(7) M-1 s-1. Irradiation of phycocyanin with red light bleaches the chromophore with low yields (approximately 0.8 x 10(-4)). Part of this bleaching is mediated by singlet oxygen produced by the irradiation of the bilin group. The low relevance of the singlet oxygen pathway is compatible with a low quantum yield (approximately 10(-3)) of free singlet oxygen production after irradiation of the protein.

[Comparative effects of policosanol and two HMG-CoA reductase inhibitors on type II hypercholesterolemia]. / Efecto comparativo de policosanol con dos inhibidores de la HMG-CoA reductasa en el tratamiento de la hipercolesterolemia tipo II.

BACKGROUND: Policosanol is a new cholesterol lowering agent derived from sugar cane. AIM: To compare the cholesterol lowering efficacy of policosanol with HMG CoA inhibitors. PATIENTS AND METHODS: Patients with a LDL cholesterol over 160 mg/dl were studied. If, after 6 weeks of diet, cholesterol persisted elevated, they were doubly blind randomized to receive policosanol 10 mg/day (55 patients), lovastatin 20 mg/day (26 patients) or simvastatin 10 mg/day (25 patients). Serum cholesterol was measured again after 8 weeks of therapy. RESULTS: Initial demographic and laboratory data were similar among treatment groups. A 24% LDL cholesterol reduction was obtained with policosanol, compared with a 22% reduction with lovastatin and a 15% reduction with simvastatin. HDL cholesterol significantly increased in patients on policosanol and did not change in the other treatment groups. Adverse effects of policosanol were mild and unspecific. No changes in hepatic enzymes were observed. CONCLUSIONS: Policosanol is a safe and effective cholesterol reducing agent.

Neural development in the marsupial frog Gastrotheca riobambae.

The expression pattern of the tyrosine kinase gene Pag in whole-mount preparations of Gastrotheca riobambae embryos and the immunostaining of embryos against the proteins vimentin, NCAM, Pax-2, Hoxd9, and antigen 2G9 allowed detection of migrating streams of cranial neural crest (NC) cells, the isthmus, the hindbrain boundaries, rhombomeres, cranial nerves, and the developing spinal cord. Expression patterns of these genes and the basic neural morphology of Gastrotheca have been conserved in comparison with other vertebrates. However, as in Xenopus, a prominent stream of migrating cranial NC cells from rhombomere 5 was found in Gastrotheca embryos. By contrast, in chick embryos, premigratory NC cells from rhombomeres 3 and 5 undergo extensive apoptosis, which suggests that in anurans, apoptosis of the cranial NC may deviate from the chick pattern. The branchial-anterior and branchial-posterior masses of cranial NC cells, that populate the gill arches, are very large in G. riobambae. We cannot distinguish whether this feature corresponds to an anuran trait related to development of the tadpole pharyngeal skeleton, or is related to development of the peculiar external bell gills of this frog. This work provides the descriptive groundwork for lineage studies of the NC in G. riobambae embryos. Gastrotheca embryos are large and flat, have prominent streams of cranial NC cells, and develop very large external bell gills. These unique characteristics may facilitate future comparative analysis of the role of apoptosis in patterning the amphibian NC cell streams, and the contribution of the NC to development of the gills.

Effects of nebulized salbutamol on respiratory mechanics in adult respiratory distress syndrome.

OBJECTIVE: To determine whether nebulized salbutamol improves the respiratory mechanics of patients with adult respiratory distress syndrome (ARDS). We also assessed the mechanisms that contribute to high respiratory system resistances during this disease. PATIENTS AND SETTING: Eleven consecutive patients with ARDS without clinical evidence of chronic obstructive pulmonary disease, admitted to a polivalent intensive care unit, and mechanically ventilated with Siemens Elema Servo C ventilator at constant inspiratory flow. METHOD: Peak airway pressure (Ppeak), airway pressure immediately after end inspiratory occlusion (P1), plateau pressure (P2) and intrinsic positive end-expiratory pressure (PEEPi) were measured at baseline condition and then 5, 15, and 30 min after 1 mg of salbutamol had been administered via a nebulizer through the endotracheal tube. Partial pressure of arterial oxygen (PaO2), heart rate (HR) and mean blood pressure (BP) were monitored and minimal respiratory system resistances (Rrs, m), additional resistances (DRrs) and static compliance (Cst) were computed. RESULTS: Between baseline and post-salbutamol, we observed changes in Ppeak, P1, P2, PEEPi and Rrs, m. As there were no significant differences between values at the different intervals during post administration, the results are described comparing baseline and 15 min post-salbutamol administration values. We found a significant decrease in Ppeak (4.9 +/- 0.8 cmH2O). P1 (3 +/- 0.6 cmH2O). P2 (2.1 +/- 0.6 cmH2O), PEEPi (1.9 +/- 0.5 cmH2O) and Rrs, m (1.9 +/- 0.3 cmH2O/1 s-1); DR, rs decreased in five patients, did not change in four and increased in two. HR, PaO2 and BP did not change. CONCLUSIONS: a) Salbutamol administered through the endotracheal tube by a nebulizer device lessens respiratory system resistances and airway and alveolar pressures, and therefore could decrease the risk of barotrauma and alveolar damage; b) high respiratory system resistances in ARDS have an increased smooth muscle tone component that can be reversible with salbutamol.

The expression of Brachyury (T) during gastrulation in the marsupial frog Gastrotheca riobambae.

Gastrulation in the marsupial frog Gastrotheca riobambae has been analyzed by the distribution of the Brachyury (T) protein. Comparison with other amphibians provides mechanistic insights, since G. riobambae develops slowly and has the most divergent mode of amphibian gastrulation, producing an embryonic disk. The T pattern indicates that the prospective mesoderm is superficial, as in many amphibians. The dorsal blastopore lip could not be identified by the expression of T, or by morphological criteria, thus it is unknown whether Gastrotheca embryos have a dorsal organizer before or after blastopore closure. The circumblastoporal and notochordal expression of T, which are temporally contiguous in Xenopus, are separated in Gastrotheca, implying that distinct regulatory mechanisms may control the expression of T in its two domains. The separation of the T pattern also indicates that involution at the blastopore is separate from notochord formation. In addition, extension of the archenteron and notochord occurs after blastopore closure, suggesting that dorsal convergence and extension have been delayed until after blastopore closure. Therefore, dorsal convergence and extension need not be the cause of blastopore closure in Gastrotheca. The separation of gastrulation events in embryos that have not been experimentally manipulated, such as those of Gastrotheca, helps in understanding the distinct nature of gastrulation processes.

Implante de prótesis peneana con conservación del tejido erectil: 10 años de experiencia / Penis prosthesis implant preserving erectil tissue: 10 years experience

Se describe la técnica de implante de prótesis peneana con conservación del tejido erectil. Con este nuevo y original procedimiento se ha operado a 410 pacientes en los últimos 10 años, obteniendo resultados hasta el momento muy buenos. Con esta cirugía se aprovecha la capacidad de tumefacción residual que todos los pacientes tienen, obteniendo una erección dinámica y más natural, que se asemeja a una respuesta erectiva normal, con lo que mejora la aceptación del procedimiento, tanto por parte del paciente como su pareja. Las complicaciones son mínimas. Una pérdida de la prótesis por infección. No hay rechazo practicamente, existe ausencia de infecciones secundaris al conservar intacto el árbol arterial intracavernoso con la indemnidad de sus arterias cavernosas y helicinas y la ausencia de tejido necrótico residual susceptible de infectarse

Trauma Raquimedular

En este estudio retrospectivo se exponen y se analizan los resultados del tratamiento quirúrgico y conservador para las luxofracturas que involucran la columna vertebral. Las fracturas de columna fueron valoradas en 152 pacientes en un período de 13 años en el Servicio de Ortopedia y Traumatología del Hospital Carlos Andrade Marín de Quito, el 80.90 por ciento de pacientes fueron intervenidos quirurgicamente, mientras que el 19.0 por ciento fueron manejados con tratamiento conservador. El promedio de tiempo al tratamiento quirúrgico fue de 11 días. Los resultados fueron evaluados de acuerdo al déficit neurológico y si eran fracturas estables o inestables o habían fragmentos que invadían canal medular con o sín déficit neurológico. En el grupo con tratamiento quirúrgico un total de 123 pacientes (80.9 por ciento) terminó en instrumentación de Harrington, fusión, alambrado, placas de Roy Camille debido a la inestabilidad de 2 a 3 columnas y si había deterioro de su estado neurológico se les realizó laminectomía. De ellos 32 pacientes (22 por ciento) recuperaron su estado neurológico, el 19.0 por ciento fueron tratados conservadoramente debido a que eran fracturas estables y poe lo tanto no había déficit neurológico.

Somitogenesis in the marsupial frog Gastrotheca riobambae.

This paper reports the first description of somitogenesis in a non-aquatic-developing amphibian, the Andean marsupial frog, Gastrotheca riobambae. This frog develops from an embryonic disk located on top of a large yolky egg, bearing some resemblance to the embryo of the chick. Besides the histological characterization of somite formation, we quantified cell number in the developing somites of Gastrotheca, Xenopus laevis and the chick. Gastrotheca was found to have a mode of somitogenesis which has previously been encountered in the aquatic-developing toad Bombina. Somitic cell number was found to be an order of magnitude higher than that of Xenopus, and approximately double that of the chick. We discuss the possible relation between mode of somitogenesis, somitic cell number, speed of development and egg size.

5S rRNA-encoding genes of the marsupial frog Gastrotheca riobambae.

The major 5S rRNA gene repeat of the marsupial frog, Gastrotheca riobambae, is 1052 bp in length. It contains a 5S rRNA gene similar to the Xenopus laevis somatic gene, two spacer regions, and a pseudogene. The G. riobambae haploid genome contains about 500 copies of this predominant repeat. This relatively low number of 5S rRNA genes is associated with a limited amplification of the 18S, 5.8S and 28S rRNA genes in oocytes and with a slow rate of early development.

Ureotelism as the prevailing mode of nitrogen excretion in larvae of the marsupial frog Gastrotheca riobambae (Fowler) (Anura, Hylidae).

1. Embryos from the pouch of the marsupial hylid frog Gastrotheca riobambae excrete urea. 2. Free-living tadpoles of G. riobambae excrete mainly urea, in comparison with tadpoles of other hylid frogs. 3. The activity of arginase is high in embryos from the pouch, and in tadpoles of G. riobambae. 4. The ureotelism of G. riobambae larvae is an adaptation for prolonged incubation in the pouch of the mother, and for development in limited amounts of water.