Unexpected metastatic pheochromocytoma - an unusual presentation

The classic triad of pheochromocytoma consists of episodic headache, sweating, and tachycardia. General clinicians should be aware, however, that this rare entity might present with a wide spectrum of clinical symptoms. We recently observed a noteworthy case of malignant pheochromocytoma where there was a lack of specific symptoms despite an advanced tumor stage. Malignancy is an important cause of mortality. Reliable diagnosis of malignancy depends upon evidence of local invasion, distant metastases, or recurrence. As in our case, new scintigraphic methods, such as 111-In-pentetreotide scintigraphy (Octreoscan), may occasionally reveal 123-I-metaiodobenzylguanidine-negative distant metastases and help to establish an early diagnosis of malignancy. Tumor size, and perhaps even biochemical profile, may be factors increasing the likelihood of a malignant process and may contribute to early identification of patients at risk.

Phenotype-genotype correlation in eight Polish patients with inherited Factor XIII deficiency: identification of three novel mutations

Inherited factor XIII (FXIII) deficiency is known as one of the most rare blood coagulation disorder in humans. In the present study, phenotype and genotype of eight FXIII deficient Polish patients from five unrelated families were compared. The patients presented with a severe phenotype demonstrated by a high incidence of intracerebral haemorrhages (seven of eight patients), haemarthrosis (six patients) and bleeding due to trauma (five patients). Introduction of regular substitution with FXIII concentrate prevented spontaneous bleeding in seven patients. In all patients, mutations within the F13A gene have been identified revealing four missense mutations (Arg77Cys, Arg260Cys, Ala378Pro, Gly420Ser), one nonsense mutation (Arg661X), one splice site mutation (IVS5-1 G>A) and one small deletion (c.499-512del). One homozygous large deletion involving exon 15 was detected by failure of PCR product. The corresponding mutations resulted in severely reduced FXIII activity and FXIII A-subunit antigen concentration, while FXIII B-subunit antigen remained normal or mildly decreased. Structural analysis demonstrated that the novel Ala378Pro mutation may cause a disruption of the FXIII catalytic triad leading to a non-functional protein which presumably undergoes premature degradation. In conclusion, the severe phenotype with high incidence of intracranial bleeding and haemarthrosis was in accordance with laboratory findings on FXIII and with severe molecular defects of the F13A gene.

Hint2 is expressed in the mitochondria of H295R cells and is involved in steroidogenesis

Hint2 belongs to the superfamily of histidine triad hydrolase enzymes. Recently, it has been shown to influence the mitochondria-dependent apoptosis occurring in hepatocytes, but its mechanism of action is still obscure. Here, we demonstrate that Hint2 is expressed in the mitochondria of H295R cells and in normal adrenals, and that this protein is involved in steroidogenesis. The presence of Hint2 in H295R cells was revealed by RT-PCR and by immunoblot analysis of subcellular fractions. The protein appeared associated with mitochondrial membranes, probably facing the interior of the organelle. Hint2 overexpression in H295R cells had no effect on pregnenolone secretion elicited by angiotensin II or K+, whereas protein silencing with specific small interfering RNA resulted in a marked reduction of the steroidogenic response. The duration of the mitochondrial calcium signal induced by angiotensin II was also reduced upon Hint2 down-regulation with small interfering RNA, but not affected after its overexpression, suggesting that under basal conditions, Hint2 is optimally expressed, and not rate limiting in steroidogenesis. Moreover, Hint2 also appeared involved in Ca2+-independent pathways leading to steroid formation. Indeed, pregnenolone formation in response to either forskolin or a hydroxyl analog of cholesterol was markedly reduced after Hint2 silencing. Calcium-dependent and calcium-independent actions of Hint2 on steroidogenesis could be related to its ability to maintain a favorable mitochondrial potential. In conclusion, these data suggest that, in H295R cells, Hint2 is required for an optimal steroidogenic response, possibly because of a particular signalling function exerted within the mitochondria and that still remains to determine at the molecular level.

Polonofilizm i polskość wśród czeskich emancypantek w drugiej połowie XIX wieku: przykład Karoliny Světlej

The awakening of national consciousness went hand in hand in Bohemia with an anxiety about national disappearance. In this context, the recourse to Pan-Slavism was for the Czechs a way to encourage themselves through the idea of belonging to a great Slavic world, while the Slavic Congress organized in Prague in 1848 was an attempt to realize this ideal. The Congress was a failure from the political point of view, but it did have some socio-cultural repercussions: notably, it served as a pretext for the advancement of women's issues in Bohemia. It is indeed in the wake of the Congress that Honorata z Wiśniowskich Zapová, a Polish women settled in Prague after her marriage to a Czech intellectual, founded, under the guise of collaboration between all Slavic women, the first women's association, as well as a (very short-lived) Czech-Polish institute, where Czech, as well as Polish girls, could get a quality education in their mother tongue. Honorata was undoubtedly the source of the polonophilia wind that seemed to blow over the Czech emancipation movement in the second half of the nineteenth century. In particular, Karolina Světlá showed in her Memoirs a great recognition for Honorata's efforts in matters of emancipation and education, and explicitly took up the challenge launched by the latter in founding another women's association and in inaugurating a school for underprivileged girls. But the tribute Světlá paid to Honorata is even more evident in her literary work, where Poland and the Polish woman (who often wears Honorata's features) play a significant role (see for example her short novel Sisters or her story A Few Days in the Life of a Prague Dandy). Světlá was probably the Czech feminist writer who, in her activities and in her work, relied most strongly on the Polish woman as a model for the Czech woman. However, she wasn't alone. In general, it was a characteristic of the Czech feminist movement of the second half of the nineteenth century to have recourse to the Polish woman and to Poland as a landmark for comparison and as a goal to be achieved.

[Meningitis (I)--differential diagnosis; aseptic and chronic meningitis].

Meningitis is the most common serious manifestation of infection of the central nervous system. Inflammatory involvement of the subarachnoid space with meningeal irritation leads to the classical triad of headache, fever, and meningism, and to a pleocytosis of the cerebrospinal fluid (CSF). Meningitis is clinically categorized into an acute and chronic disease based on the acuity of symptoms. Acute meningitis develops over hours to days, while in chronic meningitis symptoms evolve over days or even weeks. Aseptic meningitis, in which no bacterial pathogen can be isolated by routine cultures, can mimic bacterial meningitis, but the disease has a much more favorable prognosis. Many cases of aseptic meningitis are caused by viruses, primarily enteroviruses, but bacteria and noninfectious etiologies also cause meningitis with negative cultures. Symptoms of meningeal inflammation with CSF pleocytosis that persist for more than 4 weeks define the chronic meningitis syndrome. The diagnosis is based on the patient history, clinical evidence of meningitis, CSF examination, and often imaging studies. The differential diagnosis is broad, and the predominant CSF cell type can provide clues as to the underlying disease. Empiric therapy is primarily based on the age of the patient, with modifications if there are positive findings on CSF gram stain or if the patient presents with special risk factors. In patients with chronic meningitis, a definite diagnosis is often not available or delayed for days, in which case empiric therapy may have to be initiated. It is important to cover the treatable causes of meningitis, for which the outcome is poor if treatment is delayed.

Characterization of the Effect of the Mitochondrial Protein Hint2 on Intracellular Ca2+ dynamics

Hint2, one of the five members of the superfamily of the histidine triad AMP-lysine hydrolase proteins, is expressed in mitochondria of various cell types. In human adrenocarcinoma cells, Hint2 modulates Ca2+ handling by mitochondria. As Hint2 is highly expressed in hepatocytes, we investigated if this protein affects Ca2+ dynamics in this cell type. We found that in hepatocytes isolated from Hint2−/− mice, the frequency of Ca2+ oscillations induced by 1 μM noradrenaline was 150% higher than in the wild-type. Using spectrophotometry, we analyzed the rates of Ca2+ pumping in suspensions of mitochondria prepared from hepatocytes of either wild-type or Hint2−/− mice; we found that Hint2 accelerates Ca2+ pumping into mitochondria. We then resorted to computational modeling to elucidate the possible molecular target of Hint2 that could explain both observations. On the basis of a detailed model for mitochondrial metabolism proposed in another study, we identified the respiratory chain as the most probable target of Hint2. We then used the model to predict that the absence of Hint2 leads to a premature opening of the mitochondrial permeability transition pore in response to repetitive additions of Ca2+ in suspensions of mitochondria. This prediction was then confirmed experimentally.

Post-mortem whole body computed tomography of opioid (heroin and methadone) fatalities: frequent findings and comparison to autopsy

OBJECTIVE To investigate frequent findings in cases of fatal opioid intoxication in whole-body post-mortem computed tomography (PMCT). METHODS PMCT of 55 cases in which heroin and/or methadone had been found responsible for death were retrospectively evaluated (study group), and were compared with PMCT images of an age- and sex-matched control group. Imaging results were compared with conventional autopsy. RESULTS The most common findings in the study group were: pulmonary oedema (95 %), aspiration (66 %), distended urinary bladder (42 %), cerebral oedema (49 %), pulmonary emphysema (38 %) and fatty liver disease (36 %). These PMCT findings occurred significantly more often in the study group than in the control group (p < 0.05). The combination of lung oedema, brain oedema and distended urinary bladder was seen in 26 % of the cases in the study group but never in the control group (0 %). This triad, as indicator of opioid-related deaths, had a specificity of 100 %, as confirmed by autopsy and toxicological analysis. CONCLUSIONS Frequent findings in cases of fatal opioid intoxication were demonstrated. The triad of brain oedema, lung oedema and a distended urinary bladder on PMCT was highly specific for drug-associated cases of death. KEY POINTS Frequent findings in cases of fatal opioid intoxication were investigated. Lung oedema, brain oedema and full urinary bladder represent a highly specific constellation. This combination of findings in post-mortem CT should raise suspicion of intoxication.

What's in a name? Inflammatory airway disease in racehorses in training

The term 'inflammatory airway disease' (IAD) is often used to describe the syndrome of lower airway inflammation that frequently affects young racehorses in training around the world. In practice, this inflammation is generally diagnosed using a combination of endoscopic tracheal examination, including grading of amounts of mucus present and tracheal wash sampling. However, a recent consensus statement from the American College of Veterinary Internal Medicine concluded that bronchoalveolar lavage (BAL) sampling, rather than tracheal wash (TW) sampling, is required for cytological diagnosis of IAD and that tracheal mucus is not an essential criterion. However, as BAL is a relatively invasive procedure that is not commonly used on racing yards, this definition can only be applied routinely to a biased referral population. In contrast, many practitioners continue to diagnose IAD using endoscopic tracheal examination and sampling. We argue that, rather than restricting the use of the term IAD to phenotypes diagnosed by BAL, it is important to distinguish in the literature between airway inflammation diagnosed by BAL and that identified in the field using TW sampling. We suggest the use of the term brIAD for the former and trIAD for the latter. It is essential that we continue to endeavour to improve our understanding of the aetiology, pathogenesis and clinical relevance of airway inflammation identified in racehorses in training using tracheal examination and sampling. Future studies should focus on investigations of the component signs of airway inflammation.

Systemic Scuticociliatosis (Philasterides dicentrarchi) in sharks.

Scuticociliatosis is an economically important, frequently fatal disease of marine fish in aquaculture, caused by histophagous ciliated protozoa in the subclass Scuticociliatida of the phylum Ciliophora. A rapidly lethal systemic scuticociliate infection is described that affected aquarium-captive zebra sharks (Stegostoma fasciatum), Port Jackson sharks (Heterodontus portusjacksoni), and a Japanese horn shark (Heterodontus japonicus). Animals died unexpectedly or after a brief period of lethargy or behavioral abnormality. Gross findings included necrohemorrhagic hepatitis and increased volumes of celomic fluid. Histologically, 1 or more of a triad of necrotizing hepatitis, necrotizing meningoencephalitis, and thrombosing branchitis were seen in all cases, with necrotizing vasculitis or intravascular fibrinocellular thrombi. Lesions contained variably abundant invading ciliated protozoa. Molecular identification by polymerase chain reaction from formalin-fixed tissues identified these as the scuticociliate Philasterides dicentrarchi (syn. Miamiensis avidus), a novel and potentially emergent pathogen in sharks.

Linking Ah receptor mediated effects of sediments and impacts on fish to key pollutants in the Yangtze Three Gorges Reservoir, China – A comprehensive perspective

The Three Gorges Reservoir (TGR), created in consequence of the Yangtze River's impoundment by the Three Gorges Dam, faces numerous anthropogenic impacts that challenge its unique ecosystem. Organic pollutants, particularly aryl hydrocarbon receptor (AhR) agonists, have been widely detected in the Yangtze River, but only little research was yet done on AhR-mediated activities. Hence, in order to assess effects of organic pollution, with particular focus on AhR-mediated activities, several sites in the TGR area were examined applying the "triad approach". It combines chemical analysis, in vitro, in vivo and in situ investigations to a holistic assessment. Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011/2012, respectively, to identify relevant endpoints. Sediment was tested in vitro with the ethoxyresorufin-O-deethylase (EROD) induction assay, and in vivo with the Fish Embryo Toxicity Test and Sediment Contact Assay with Danio rerio. Activities of phase I (EROD) and phase II (glutathione-S-transferase) biotransformation enzymes, pollutant metabolites and histopathological alterations were studied in situ in P. vachellii. EROD induction was tested in vitro and in situ to evaluate possible relationships. Two sites, near Chongqing and Kaixian city, were identified as regional hot-spots and further investigated in 2013. The sediments induced in the in vitro/in vivo bioassays AhR-mediated activities and embryotoxic/teratogenic effects - particularly on the cardiovascular system. These endpoints could be significantly correlated to each other and respective chemical data. However, particle-bound pollutants showed only low bioavailability. The in situ investigations suggested a rather poor condition of P. vachellii, with histopathological alterations in liver and excretory kidney. Fish from Chongqing city exhibited significant hepatic EROD induction and obvious parasitic infestations. The polycyclic aromatic hydrocarbon (PAH) metabolite 1-hydroxypyrene was detected in bile of fish from all sites. All endpoints in combination with the chemical data suggest a pivotal role of PAHs in the observed ecotoxicological impacts.

El significado aritmológico de la Tríada y sus Proyecciones Filosófico-Religiosas

Bertrand Russell dio una solución lógica general a la definición de los números caracterizando al número tres como la clase que es correspondiente a todas las clases biunívocas con los grupos de tres. Para Frege la definición del número era una de las cruces de la comprensión de la aritmética. Hegel, por su parte, bajo el impulso de la triplicidad kantiana de los juicios sintéticos, teoréticos y prácticos y la influencia de la concepción trinitaria cristiana advertía que la contraposición de los opuestos al no ser contradictoria permitía el desarrollo deviniente. La aritmología pitagórica sobre los números naturales destacó la definición del tres caracterizada por su naturaleza de mediedad. Retomando estas bases de pura inteligibilidad y las especulaciones gnósticas sobre la tríada mostraremos sus proyecciones filosófico-religiosas.

Arte, política y espacio : Una revisión crítica desde el posestructuralismo

En esta tesis proponemos realizar un aporte al campo de los estudios sociopolíticos del arte, a partir de pensar la relación entre arte, política y espacio, teniendo especialmente en cuenta la centralidad del mismo en autores posestructuralistas que abordan la relación entre arte y política. Para ello, hacemos foco en los análisis de la relación entre arte y política de Jacques Rancière, Chantal Mouffe y Nelly Richard, como estrategia para analizar y establecer a posteriori el lugar que ocupa el espacio. Asimismo, tomamos, también desde el posestructuralismo, los desarrollos efectuados por Doreen Massey, sobre la construcción social del espacio y las dinámicas de poder que lo atraviesan. A su vez, recuperamos los aportes de Henri Lefebvre y Milton Santos para adentrarnos a la problemática de la producción social del espacio. En síntesis, apuntamos a producir un análisis que considere al espacio como una construcción social y de carácter político, atravesado por relaciones de poder, cuya presencia en las acciones artísticas no es sólo contextual, por lo que excede a la idea de simple emplazamiento o escenario donde transcurren los hechos. Así, problematizamos un vacío en relación a lo que hemos llamado trinomio entre arte, política y espacio contribuyendo a generar una perspectiva compleja que integre estos tres conceptos. Para la realización de la tesis planteamos, como estrategia metodológica, una revisión crítica de la bibliografía seleccionada de los autores ya mencionados. Consideramos que a partir del estudio y análisis del material bibliográfico, contribuimos a generar una perspectiva que integra arte, política y espacio, que será productiva para el desarrollo de futuras investigaciones dirigidas al estudio de casos de artistas y grupos de artistas de diverso origen y temporalidad. Asimismo, incorporamos a los argumentos y terminologías de los autores aquí trabajados, obras y prácticas artísticas, no como mera ilustración, sino estableciendo un diálogo que potencie el ejercicio crítico y la reflexión teórica

Bajo los adoquines está la Pachamama : Territorialidad andina en el Gran La Plata [2008-2011]

Desde hace aproximadamente 20 años, se está viviendo un resurgimiento del movimiento indígena a nivel mundial y continental. El territorio juega un papel esencial para las numerosas organizaciones y comunidades que lo componen, en tanto articula el accionar de estos sujetos al espacio en un sentido procesual y relacional, a través de una concepción en la que la tríada territorio-territorialidad-territorialización, niega la dualidad cartesiana entre materia y espíritu y afirma que toda apropiación material es a la vez simbólica. Según la Encuesta Complementaria de Pueblos Indígenas 2004-2005, complementaria del Censo Nacional de Población, Hogares y Viviendas 2001 del INdEC, el 54 de las 600.329 personas que se autoreconocen como parte de alguno de los más de treinta pueblos aborígenes que habitan en Argentina, se encuentra en áreas urbanas. El interés de este trabajo es el entender cuáles son las modalidades de apropiación material y simbólica del espacio que llevan adelante la Organización Quechua-Aymara Hijos del Cóndor [Kunthurpa Churinkuna] en conjunto con la Academia Mayor de la Lengua Quechua de Cusco-Filial Regional Internacional "Berisso" [Qheswasimi Jamutána Kuraq Suntur Qosqo-Perusuyu], y la Comunidad Qolla Gran La Plata, todas pertenecientes al universo cultural andino, y activas en el ámbito de la capital bonaerense. Es decir, qué territorialidad específica construyen en el espacio urbano, en función de la recreación de su cultura ancestral [analizada a través del enfoque del control cultural], y atendiendo a su relación con sus estrategias políticas y sus condiciones socioeconómicas, que se ponen en juego en la configuración de determinados espacios de socialización. Se trata de una investigación que emplea el método etnográfico, con técnicas tales como la observación participante y la entrevista en profundidad

Arte, política y espacio : Una revisión crítica desde el posestructuralismo

En esta tesis proponemos realizar un aporte al campo de los estudios sociopolíticos del arte, a partir de pensar la relación entre arte, política y espacio, teniendo especialmente en cuenta la centralidad del mismo en autores posestructuralistas que abordan la relación entre arte y política. Para ello, hacemos foco en los análisis de la relación entre arte y política de Jacques Rancière, Chantal Mouffe y Nelly Richard, como estrategia para analizar y establecer a posteriori el lugar que ocupa el espacio. Asimismo, tomamos, también desde el posestructuralismo, los desarrollos efectuados por Doreen Massey, sobre la construcción social del espacio y las dinámicas de poder que lo atraviesan. A su vez, recuperamos los aportes de Henri Lefebvre y Milton Santos para adentrarnos a la problemática de la producción social del espacio. En síntesis, apuntamos a producir un análisis que considere al espacio como una construcción social y de carácter político, atravesado por relaciones de poder, cuya presencia en las acciones artísticas no es sólo contextual, por lo que excede a la idea de simple emplazamiento o escenario donde transcurren los hechos. Así, problematizamos un vacío en relación a lo que hemos llamado trinomio entre arte, política y espacio contribuyendo a generar una perspectiva compleja que integre estos tres conceptos. Para la realización de la tesis planteamos, como estrategia metodológica, una revisión crítica de la bibliografía seleccionada de los autores ya mencionados. Consideramos que a partir del estudio y análisis del material bibliográfico, contribuimos a generar una perspectiva que integra arte, política y espacio, que será productiva para el desarrollo de futuras investigaciones dirigidas al estudio de casos de artistas y grupos de artistas de diverso origen y temporalidad. Asimismo, incorporamos a los argumentos y terminologías de los autores aquí trabajados, obras y prácticas artísticas, no como mera ilustración, sino estableciendo un diálogo que potencie el ejercicio crítico y la reflexión teórica

Bajo los adoquines está la Pachamama : Territorialidad andina en el Gran La Plata [2008-2011]

Desde hace aproximadamente 20 años, se está viviendo un resurgimiento del movimiento indígena a nivel mundial y continental. El territorio juega un papel esencial para las numerosas organizaciones y comunidades que lo componen, en tanto articula el accionar de estos sujetos al espacio en un sentido procesual y relacional, a través de una concepción en la que la tríada territorio-territorialidad-territorialización, niega la dualidad cartesiana entre materia y espíritu y afirma que toda apropiación material es a la vez simbólica. Según la Encuesta Complementaria de Pueblos Indígenas 2004-2005, complementaria del Censo Nacional de Población, Hogares y Viviendas 2001 del INdEC, el 54 de las 600.329 personas que se autoreconocen como parte de alguno de los más de treinta pueblos aborígenes que habitan en Argentina, se encuentra en áreas urbanas. El interés de este trabajo es el entender cuáles son las modalidades de apropiación material y simbólica del espacio que llevan adelante la Organización Quechua-Aymara Hijos del Cóndor [Kunthurpa Churinkuna] en conjunto con la Academia Mayor de la Lengua Quechua de Cusco-Filial Regional Internacional "Berisso" [Qheswasimi Jamutána Kuraq Suntur Qosqo-Perusuyu], y la Comunidad Qolla Gran La Plata, todas pertenecientes al universo cultural andino, y activas en el ámbito de la capital bonaerense. Es decir, qué territorialidad específica construyen en el espacio urbano, en función de la recreación de su cultura ancestral [analizada a través del enfoque del control cultural], y atendiendo a su relación con sus estrategias políticas y sus condiciones socioeconómicas, que se ponen en juego en la configuración de determinados espacios de socialización. Se trata de una investigación que emplea el método etnográfico, con técnicas tales como la observación participante y la entrevista en profundidad