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.

Intense PEGylation of Enzyme Surfaces: Relevant Stabilizing Effects.

This chapter describes the physicochemical coating of the surface of immobilized enzymes with a dense layer of polyethylene glycol (PEG) to improve enzyme stability. One hypothesis is that a dense, viscous, polar PEG layer around the enzyme would enhance enzyme thermal stability, while still providing access to the active site. PEG groups were attached by using aldehyde-dextran polymers, the dextran polymers are in turn attached to the enzyme surface that have been enriched with excess primary amino groups. The enzymes themselves were initially attached onto porous solids such that they may be separated easily from the reaction mixtures for easy downstream processing and that they may be recycled to reduce the cost of the biocatalyst. The hierarchical modification of enzyme surface with three different sublayers, under chemical design, provided a rational control at several structural levels. Few methods for increasing the number of amino groups on the surface of the enzyme are described: (a) chemical amination of carboxyl residues and (b) coating of the enzyme surface with cationic polymers containing a high percentage of primary amines. Reliable protocols for the PEGylation of four different enzymes are described here. For example, lipases from Thermomyces lanuginosa, Candida antarctica B, and Rhizomucor miehei attached to octyl sepharose and chemically modified via PEGylation are stabilized from 7- to 50-fold when compared to the stability of the corresponding unmodified enzyme. A derivative of endoxylanase from Trichoderma reesei, immobilized by multipoint covalent attachment on glyoxyl agarose, is stabilized by 50-fold. Very likely, the PEG layer generated a dense, high viscosity medium surrounding the enzyme surface and this increase in viscosity around the enzyme microenvironment resists distortion of enzyme structure by heat or other denaturing agents.

Neuroblastoma cells injected into experimental mature teratoma reveal a tropism for embryonic loose mesenchyme.

Embryonic neural tumors are responsible for a disproportionate number of cancer deaths in children. Although dramatic improvements in survival for pediatric malignancy has been achieved in previous years advancements seem to be slowing down. For the development of new enhanced therapy and an increased understanding of the disease, pre-clinical models better capturing the neoplastic niche are essential. Tumors of early childhood present in this respect a particular challenge. Here, we explore how components of the embryonic process in stem­cell induced mature teratoma can function as an experimental in vivo microenvironment instigating the growth of injected childhood neuroblastoma (NB) cell lines. Three human NB cell lines, IMR-32, Kelly and SK-N-BE(2), were injected into mature pluripotent stem cell­induced teratoma (PSCT) and compared to xenografts of the same cell lines. Proliferative NB cells from all lines were readily detected in both models with a typical histology of a poorly differentiated NB tumor with a variable amount of fibrovascular stroma. Uniquely in the PSCT microenvironment, NB cells were found integrated in a non­random fashion. Neuroblastoma cells were never observed in areas with well-differentiated somatic tissue i.e. bone, muscle, gut or areas of other easily identifiable tissue types. Instead, the three cell lines all showed initial growth exclusively occurring in the embryonic loose mesenchymal stroma, resulting in a histology recapitulating NB native presentation in vivo. Whether this reflects the 'open' nature of loose mesenchyme more easily giving space to new cells compared to other more dense tissues, the rigidity of matrix providing physical cues modulating NB characteristics, or if embryonic loose mesenchyme may supply developmental cues that attracted or promoted the integration of NB, remains to be tested. We tentatively hypothesize that mature PSCT provide an embryonic niche well suited for in vivo studies on NB.

PROX1 is a predictor of survival for gliomas WHO grade II.

BACKGROUND: The clinical course of World Health Organisation grade II gliomas remains variable and their time point of transformation into a more malignant phenotype is unpredictable. Identification of biological markers that can predict prognosis in individual patients is of great clinical value. PROX1 is a transcription factor that has a critical role in the development of various organs. PROX1 has been ascribed both oncogenic and tumour suppressive functions in human cancers. We have recently shown that PROX1 may act as a diagnostic marker for high-grade gliomas. The aim of this study was to address the prognostic value of PROX1 in grade II gliomas. METHODS: A total of 116 samples were evaluated for the presence of PROX1 protein. The number of immunopositive cells was used as a variable in survival analysis, together with established prognostic factors for this patient group. RESULTS: Higher PROX1 protein was associated with poor outcome. In the multivariate analysis, PROX1 was identified as an independent factor for survival (P=0.024), together with the presence of mutated isocitrate dehydrogenase 1 R132H protein, and with combined losses of chromosomal arms 1p/19q in oligodendrocytic tumours. CONCLUSION: PROX1 is a novel predictor of survival for grade II gliomas.

Further studies on the frequency and length of the glandulo-metaplastic esophageal mucosa in baboons.

BACKGROUND: In previous studies, the length of the glandulo-metaplastic esophageal mucosa (GMEM) at the gastroesophageal junction was assessed in a selected group of baboons. In this study, the length of the GMEM was measured in the entire esophagus in a cohort of unselected adult baboons. MATERIALS AND METHODS: In 15 female baboons, the entire esophagus was removed en bloc at autopsy, from the tongue to the angle of His. No part of the stomach was included. The length of GMEM was measured using a calibrated ocular microscale. RESULTS: GMEM was found in 11 out of the 15 esophagi. The total length of GMEM recorded in the 11 cases was 115 mm (mean 10.5 mm, range 1-45 mm). The mean age for animals with GMEM was 15.5 years (range 7-32 years) and for animals without GMEM was 14.0 years (range 7-20 years); the difference was non-significant (p<0.6). No significant association was found between the length of the GMEM and the age of the animals (p<0.6). CONCLUSION: This study substantiates the notion that GMEM in baboons is a postnatal physiological adaptative process of the esophageal mucosa to daily regurgitation with rumination of gastric juices of low pH. The GMEM apparently progresses upwards, along the esophageal mucosa. The baboon might be an excellent animal model to study the series of histological events that take place in the distal esophagus under the influence of protracted gastroesophageal reflux.

[Displacement and isolation. Mental illness in the city of Medellín. 1878-1930]. / Desplazamiento y aislamiento. Alienados mentales en la cuidad de Medellín. 1878-1930.

The observation in the city of Medellín within the framework of urban history generated a surprising picture of subjects in hygiene and public health, among which we found the case of mental illness and the control systems proposed by civilian authorities and doctors. In Medellín, between 1880 and 1950, the modernization process went on, turning its pole of attraction on population displacements to the interior of the province of Antioch. As a result of Railroad I, there was a massive mobility of population from the neighboring towns, including some mentally ill people. At the end of the 19th century, the authorities created a house of asylum for these people, which became the Mental Hospital in the middle of the 20th century. The isolation of the mentally ill people reports both medical authority and the beginning of the constitution process and institutionalization of the psychopathology and medicalization of mental disease in Antioquia at the beginning of the 20th century.

Inhibitors of mammalian target of rapamycin downregulate MYCN protein expression and inhibit neuroblastoma growth in vitro and in vivo.

Mammalian target of rapamycin (mTOR) has been shown to play an important function in cell proliferation, metabolism and tumorigenesis, and proteins that regulate signaling through mTOR are frequently altered in human cancers. In this study we investigated the phosphorylation status of key proteins in the PI3K/AKT/mTOR pathway and the effects of the mTOR inhibitors rapamycin and CCI-779 on neuroblastoma tumorigenesis. Significant expression of activated AKT and mTOR were detected in all primary neuroblastoma tissue samples investigated, but not in non-malignant adrenal medullas. mTOR inhibitors showed antiproliferative effects on neuroblastoma cells in vitro. Neuroblastoma cell lines expressing high levels of MYCN were significantly more sensitive to mTOR inhibitors compared to cell lines expressing low MYCN levels. Established neuroblastoma tumors treated with mTOR inhibitors in vivo showed increased apoptosis, decreased proliferation and inhibition of angiogenesis. Importantly, mTOR inhibitors induced downregulation of vascular endothelial growth factor A (VEGF-A) secretion, cyclin D1 and MYCN protein expression in vitro and in vivo. Our data suggest that mTOR inhibitors have therapeutic efficacy on aggressive MYCN amplified neuroblastomas.

Frequency of epithelioid granulomas in colonoscopic biopsy specimens from paediatric and adult patients with Crohn's colitis.

AIMS: To test the assumption that epithelioid granulomas found in colonoscopic biopsy specimens in patients with Crohn's colitis are markers of a different clinical behaviour. METHODS: Sections from colonoscopic biopsy specimens from 352 consecutive patients (119 children and 233 adults) were investigated. RESULTS: A total of 1117 colonoscopies were performed: 293 in children (mean 2.46 per patient) and 824 in adults (mean 3.53 per patient) (p<0.05). Granulomas at initial colonoscopy were recorded in 67.2% (43/64) of children and 65.9% (27/41) of adults (p>0.6), and at subsequent colonoscopies in 53.8% (64/119) of children and 17.6% (41/233) of adults (p<0.05). Surgical intervention was required in 6.3% (4/64) of the children having previous granuloma, but also in 14.5% (8/55) of those without previous granuloma, the rate for operated adults being 26.8% (11/41) and 24.5% (47/192), respectively (p>0.6). CONCLUSIONS: Granulomas in entry and/or in subsequent colonoscopic biopsy specimens in patients with Crohn's colitis did not predict the need for subsequent surgical intervention. The fact that the frequency of granulomas was significantly higher in children than in adults with Crohn's colitis (despite a higher mean number of colonoscopic biopsies in adults), and that granulomas were present in colonoscopic biopsy specimens but not in the subsequent surgical specimens from 50% of the paediatric and 36% of the adult patients strengthen the conviction that granulomas in Crohn's colitis might evolve or regress at different time intervals during the course of the disease. This behaviour would reflect a particular immunological reaction, an epiphenomenon from immature tissues-as in children-when challenged by the so far elusive aetiological agent responsible for Crohn's disease.

Evolución temporal de las plaquetas y los anticuerpos antiplaquetarios en pacientes de área endémica con malaria no complicada / Temporal evolution of platelets and anti-platelets antibodies in patients of endemic area with non complicated malaria

Objetivo: evaluar plaquetas y anticuerpos antiplaquetarios IgG Ac-Pl (medidos por citometría de flujo) en pacientes de Turbo (Antioquia, Colombia) con paludismo no complicado. Metodología: estudio descriptivo, prospectivo y longitudinal de 45 pacientes (14-67 años). Treinta enfermos se siguieron 7 días. Resultados: A) Pretratamiento: hubo trombocitopenia malárica (TM) en 71% y Ac-Pl en 33%, con asociación significativa entre TM y Ac-Pl. La TM no se asocia con zona de residencia, haber tenido malaria en último año ni especie actual de Plasmodium, pero si con sexo (hombres) (p = 0,02078195), pero la concentración de Ac-Pl es similar en hombres y mujeres. Igualmente, la cantidad de plaquetas es estadísticamente igual entre los valores de las variables anteriores. La presencia de Ac-Pl no se relacionó con las anteriores variables. Hay baja e inversa correlación lineal entre plaquetas y Ac-Pl (r = -0,342 (p = 0,02310). B) Durante el seguimiento, la regresión lineal múltiple entre plaquetas y edad, años de residencia, número de episodios de malaria en el último año, parasitemia (expresada logarítmicamente) y concentración de Ac-Pl demostró que ningún coeficiente es significativo y la máxima explicación lograda (17%) la dan la parasitemia y los Ac-Pl. El mismo análisis entre Ac-Pl y edad, años de residencia en la zona, número de episodios de malaria en el último año, parasitemia (expresada logarítmicamente) demostró que las tres primeras explican 38% de los cambios en Ac-Pl, mientras que los episodios de malaria y el tiempo de residencia en la zona explican el 28%

Aim: To evaluate the number of platelets and the title of anti-platelet antibodies IgG Ac-PI (by flow cytometry) in patients with non-complicated malaria. Methods: Descriptive, prospective and longitudinal study from 45 patients (aged among 14-67). Thirty patients were followed during 7 days. Results: A) Pretreatment: it was found malarial thrombocytopenia (MT) in 71 % and significant association between MT and Ac-PI in 33 %. MT was not associated to residence zone, to have had malaria in the last year and Plasmodium species but sex associated (males, p= 0,02078195), although, the Ac-PI titers of male and female was similar. Correspondingly, the number of platelets was statistically similar to the values of above variables. There was a low and an inverse lineal correlation between platelets and titres of Ac-P1 (r= -0,342 (p= 0,02310)). B) During the following, multiple linear regression among platelets, age, years of residence in the zone, number of malaria episodes in the last year, parasitaemia (logarithmically expressed) and Ac-P1 titers showed no significant coefficient and the maximum explanation achieved (17%) was parasitaemia and Ac-P1 titers. Similar analysis among Ac-P1 and age, years of residence in the zone number of malaria episodes in the last year, parasitaemia (logarithmically expressed) showed that the first three explain 38 % of the changes in Ac-P1, whereas malaria episodes and years of residence in the zone explain 28%

Bronchogenic gastric cyst. A case report.

A case of congenital bronchogenic cyst in the gastric mucosa is presented. The cyst was lined by pseudostratified epithelium and covered with ciliated cells. Congenital bronchogenic cysts should be differentiated from acquired gastric cysts lined with ciliated metaplastic cells that evolve as a result of environmental factors.

[Temporal evolution of platelets and anti-platelet antibodies in patients of endemic area with non complicated malaria]. / Evolución temporal de las plaquetas y los anticuerpos antiplaquetarios en pacientes de área endémica con malaria no complicada.

AIM: To evaluate the number of platelets and the title of anti-platelet antibodies IgG Ac-PI (by flow cytometry) in patients with non-complicated malaria. METHODS: Descriptive, prospective and longitudinal study from 45 patients (aged among 14-67). Thirty patients were followed during 7 days. RESULTS: A) Pretreatment: it was found malarial thrombocytopenia (MT) in 71 % and significant association between MT and Ac-PI in 33 %. MT was not associated to residence zone, to have had malaria in the last year and Plasmodium species but sex associated (males, p= 0.02078195), although, the Ac-PI titers of male and female was similar. Correspondingly, the number of platelets was statistically similar to the values of above variables. There was a low and an inverse lineal correlation between platelets and titres of Ac-P1 (r= -0.342 (p= 0.02310)). B) During the following, multiple linear regression among platelets, age, years of residence in the zone, number of malaria episodes in the last year, parasitaemia (logarithmically expressed) and Ac-P1 titers showed no significant coefficient and the maximum explanation achieved (17%) was parasitaemia and Ac-P1 titers. Similar analysis among Ac-P1 and age, years of residence in the zone number of malaria episodes in the last year, parasitaemia (logarithmically expressed) showed that the first three explain 38 % of the changes in Ac-P1, whereas malaria episodes and years of residence in the zone explain 28%.

Anafilaxia / Anaphylaxis

Las reacciones alérgicas fatales se describen desde hace más de 4.500 años (1), pero sólo desde el siglo pasado se empezó a comprender su fisiopatología. En 1902, Portier y Richet describieron una reacción sistémica fatal en algunos de sus animales de experimentación al inyectar repetitivamente una proteína de anémona marina, previamente tolerada (2); este fenómeno se denominó anafilaxia, para distinguirlo de la profilaxis (inyección de productos biológicos para la prevención de enfermedades).Hoy se define la anafilaxia como una reacción sistémica de hipersensibilidad inmediata, mediada por inmunoglobulina E (IgE), con liberación de mediadores proinflamatorios por los mastocitos y basófilos. La anafilaxia posee dos fases, la primera de sensibilización y la segunda efectora, como respuesta al reingreso del alergeno. El término reacción anafilactoide se refiere a un evento clínico similar, no mediado por IgE (3).Los informes clínicos iniciales sobre anafilaxia (4) mostraron una proporción elevada de casos tras la administración de suero equino utilizado en las antitoxinas para difteria y tétanos (3). Desde hace más de 4.000 años los venenos de Himenópteros son desencadenantes frecuentes de anafilaxia y aún hoy siguen siendo un problema clínico de importancia; se estima que en los Estados Unidos se generan 40 muertes al año por esta causa.El descubrimiento de la penicilina y su uso masivo después de la segunda guerra mundial generó un nuevo agente causal de anafilaxia. El primer caso fatal inducido por penicilina se notificó en 1949 (5); el uso extensivo de esta droga y su presencia en sustancias insospechadas (6) (ejemplo: la leche) fue responsable de numerosos casos fatales con una mortalidad estimada entre 100 y 500 casos por año en los Estados Unidos (3,7-9).

[Water pipelines conduits and urban sanitation in Cartagena in the beginning of the twentieth century]. / Los circuitos del agua y la higiene urbana en la ciudad de Cartagena a comienzos del siglo XX.

Throughout its history, Cartagena de Indias, a seaport in the Colombian Caribbean, has been handicapped for not offering salubrious conditions to its people and visitors. The lack of an aqueduct and a sewerage system was an impairment to progress. For nearly forty years (1890-1930) these problems have caused a myriad of medical discourses formulated by scientists, technicians and politicians. Cartagena's contribution to solve the sanitation problem in cities has consisted in making use of engineers' knowledge. The construction of urban facilities in the beginning of the twentieth century required a more technical knowledge, one which would advance a comprehensive solution to the water problem, ensure sufficient supply and efficient drainage. Thus, in the last turn of the century, the medical doctor is no longer the only authoritative voice when it comes to the management of urban life. The construction works which require an engineer, involving him in public health, have drawn a distinction between "hygiene" and "sanitary science".

Presión arterial en niños de los 4 a 14 años Medellín – Colombia / Arterial pressure in children from 4 to 14 years of age. Medellín, Colombia. 1991

La hipertensión arterial es un problema de salud pública y su detección temprana es fundamental para evitar sus posibles consecuencias. Se realizó un estudio de tipo observacional, descriptivo, en la ciudad de Medellín. El objetivo del estudio fue cuantificar los valores de presión arterial en niños escolares, entre 4 ya14 años de edad, pertenecientes a entidades educativas de la ciudad. La muestra fue de 1.200 niños; 584 mujeres y 616 hombres. Se siguieron los parámetros recomendados por el 2º Task Forceo n Blood Pressure y la Organización Mundial de la Salud. Se registro al presión arterial con esfingomanómetro de mercurio, tomando como presión arterial sistólica el primer ruido de Korotkoff o aparición del sonido, como presión arterial diastólica A, el apagamiento o cuarta (IV) fase y la presión arterial diastólica B, la desaparición o quinta fase...

Trasplante simultaneo de pancreas y rinon con pancreaticoduodenocistostomia / Simultaneous kidney and pancreas transplantation with pancreatic duodedum cystostomy

Se presentan 4 casos de trasplante simultaneo de pancreas y rinon con pancreaticoduodenocistostomia. El caso numero 1 se constituyo en el primer trasplante de este tipo realizado en Colombia, el 26 de marzo de 1988 en un paciente de 36 anos quien desde los 17 sufria una diabetes mellitus tipo I, y presentaba una insuficiencia renal terminal. Despues del trasplante estuvo insulinoindependiente por 3 semanas; la funcion renal no se recupero y fallecio el 21 de abril de 1988. El caso numero 2 es el de un paciente de 38 anos quien desde los 18 anos de edad sufria una diabeles millitus tipo I, y durante los ultimos 10 anos presentaba una retinopatia diabetica, asociada, hace 8 anos, con insuficiencia renal cronica. El 1 de noviembre de 1988 se le practico rasplante simultaneo de pancreas y rinon; 17 meses mas tarde se encuentra insulinoindependiente y con buena funcion renal. El caso numero 3 es el de un paciente de 36 anos quien tenia diabetes millitus tipo I durante los ultimos 18 anos, con falla renal desde hace 1 1/2 ano, a quien el 25 de septiembre de 1989 se le practico trasplante simultaneo de pancreas y rinon; 7 meses mas tarde se encuentra insulino independiente y con buena funcion renal. El caso 4 fue un paciente de 36 anos con diabetes tipo I, con hipertension arterial, retinopatia grado III e insuficiencia renal cronica. El 27 de marzo de 1990 se le trasplantaron simultaneamente el pancreas y un rinon de un nino de 9 anos con resultados hasta el momento satisfactorios; se halla insulinindependiente, bajo terapia triconjugada de inmunosupresion

Antigenic variation during persistent infection by equine infectious anemia virus, a retrovirus.

The recurrent nature of equine infectious anemia has been attributed to relatively rapid antigenic variations in equine infectious anemia virus (EIAV) during persistent infection under selective immune pressures. This model was tested by serological and biochemical analysis of virus isolates recovered from separate febrile episodes in two experimentally infected ponies. Neutralization assays employing immune sera from the experimentally infected ponies demonstrated that distinct antigenic strains of virus predominate during sequential febrile episodes in a single pony. Analysis of the test strains of EIAV by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed varying electrophoretic mobilities for the respective virion glycoproteins gp90 and gp45. Furthermore, peptide mapping comparisons demonstrated structural variations between the gp90 components of the various strains. In contrast, the respective internal proteins of the virus strains displayed identical electrophoretic mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and, in general, produced identical tryptic peptide maps. The observed differences in glycoprotein electrophoretic mobility and peptide maps were highly reproducible and did not vary with repeated passage of the virus strains in cell culture. Thus, these results demonstrate the occurrence of glycoprotein-specific structural variations during persistent infection by EIAV and support the concept of antigenic variation in this retrovirus. This capacity to alter envelope glycoprotein structure, previously reported for visna virus, may represent an important mechanism of retrovirus persistence in the presence of immune responses by the animal host.

Etiologia del hipotiroidismo. / The etiology of hypothyroidism

Se revisa extensamente la etiologia del hipotiroidismo, su incidencia, algumas de sus muchas clasificaciones y su evolucion, haciendo enfasis en los casos transitorios y en las causas conocidas que determinan esta reversibilidad. Se revisa exhaustivamente la clasificacion que divide el hipotiroidismo en 4 variedades bien conocidas: primario (tiroideo), secundario (hipofisiario), terciario (hipotalamico) y en periferico y se discriminan las entidades o factores responsables de cada una de estas variantes. Por ultimo, se mencionaron otros hipotiroidismos de etiologia mixta o sin clasificar