ABSTRACT It is essential to prioritize the decannulation of tracheostomized patients. A successful procedure could avoid prolonged hospital stay. Accordingly, there could be a reduction in mortality. Removing the tracheotomy cannula is a very controversial issue, because there are different types of strategies and approaches to do so. The prolonged use of the cannula must be avoided, since it entails different complications such as tracheal malacia, tracheal stenosis, tracheoesophageal fistula, and functionally altered swal lowing and phonation; thus, it is very important to be able to know exactly which are the variables that need to be measured before a patient is decannulated. Several pub lished studies disagree on which are the best indicators that should be observed to be successful. So, the objective of this review was to analyze which are the most effective target variables when performing the decannulation.

RESUMEN Es imprescindible poder priorizar la decanulación de los pacientes traqueostomizados. El éxito en el procedimiento podría evitar estadías hospitalarias prolongadas y, por consiguiente, llegar a disminuir la mortalidad. La retirada de la cánula de traqueosto mía es un tema muy controversial, dado que, para lograrla, existen diferentes tipos de abordajes y estrategias. Teniendo en cuenta que su uso prolongado debe ser evita do, ya que conlleva a diferentes complicaciones, como traqueomalacia, estenosis tra queal, fistula traqueo-esofágica, alteraciones funcionales en la deglución y la fonación, es de suma importancia poder conocer con exactitud cuáles son las variables que mensurar para que el paciente pueda ser decanulado. Diversos trabajos publicados difieren en cuáles son los mejores indicadores que deben ser observados para lograr el éxito. Por lo tanto, el objetivo de la presente revisión es analizar cuáles son las va riables objetivables con mayor eficacia al momento de llevar a cabo la decanulación.

RESUMEN Es imprescindible poder priorizar la decanulación de los pacientes traqueostomizados. El éxito en el procedimiento podría evitar estadías hospitalarias prolongadas y, por consiguiente, llegar a disminuir la mortalidad. La retirada de la cánula de traqueosto mía es un tema muy controversial, dado que, para lograrla, existen diferentes tipos de abordajes y estrategias. Teniendo en cuenta que su uso prolongado debe ser evita do, ya que conlleva a diferentes complicaciones, como traqueomalacia, estenosis tra queal, fistula traqueo-esofágica, alteraciones funcionales en la deglución y la fonación, es de suma importancia poder conocer con exactitud cuáles son las variables que mensurar para que el paciente pueda ser decanulado. Diversos trabajos publicados difieren en cuáles son los mejores indicadores que deben ser observados para lograr el éxito. Por lo tanto, el objetivo de la presente revisión es analizar cuáles son las va riables objetivables con mayor eficacia al momento de llevar a cabo la decanulación.

ABSTRACT It is essential to prioritize the decannulation of tracheostomized patients. A successful procedure could avoid prolonged hospital stay. Accordingly, there could be a reduction in mortality. Removing the tracheotomy cannula is a very controversial issue, because there are different types of strategies and approaches to do so. The prolonged use of the cannula must be avoided, since it entails different complications such as tracheal malacia, tracheal stenosis, tracheoesophageal fistula, and functionally altered swal lowing and phonation; thus, it is very important to be able to know exactly which are the variables that need to be measured before a patient is decannulated. Several pub lished studies disagree on which are the best indicators that should be observed to be successful. So, the objective of this review was to analyze which are the most effective target variables when performing the decannulation.

As Porfirias são doenças metabólicas decorrentes de falhas na biossíntese do Hemo, caracterizadas por um padrão específico de acumulação e excreção de intermediários responsáveis de sua patofisiologia. Nas Porfirias Agudas, o excesso de ácido δ-aminolevulínico (ALA) produz uma sintomatologia neuroabdominal associada ao dano oxidativo por formação de espécies reativas de oxigênio (ROS), decorrentes da auto-oxidação do ALA. Nas Cutâneas a sintomatologia é produto da acumulação de porfirinas, que como o ALA, induzem a formação de ROS. Seu desencadeamento precipita-se por fatores endógenos (jejum, estresse, hormônios) e/ou exógenos (fármacos), especialmente alguns anestésicos. Apresenta-se uma revisão dos estudos bioquímicos e genéticos em pacientes com diferentes Porfirias obtidos no Centro de Investigações de Porfirias e Porfirinas (CIPYP), durante os últimos 38 anos, que permitiram ampliar o conhecimento sobre as bases moleculares destas patologias. Descrevem-se as conquistas resultantes do uso de modelos experimentais de Porfiria, induzida farmacológica ou geneticamente, que contribuíram à classificação de algumas drogas como proibidas para pacientes com Porfiria. Afinal, as porfirinas geradoras de ROS e, por conseguinte, indutoras de morte celular têm sua aplicação para combater infecções por organismos hemo-deficientes como Trypanosoma cruzi e também ser utilizadas como fotossensibilizadores na terapia fotodinâmica (TFD).

Porphyrias comprise a group of metabolic disorders of the heme biosynthesis pathway resulting in a specific accumulation and excretion of intermediates which are responsible for their pathophysiology. Acute porphyrias are characterized by acute neurovisceral symptoms due to the overproduction and accumulation of d-aminolevulinic acid (ALA) which leads to an oxidative damage resulting from the formation of reactive oxygen species (ROS). In cutaneous porphyrias, the symptomatology is a result of porphyrin accumulation which also induces ROS moulding. In both cases, their clinical signs are precipitated by endogenous factors (stress, hormones, low calories intake) and/or exogenous drugs, in particular some anaesthetics. A review of the biochemical and genetic results obtained from patients with different porphyrias, diagnosed at the CIPYP during the last 38 years is presented here, aimed at obtaining additional evidence about the molecular nature of these disorders. The achievements obtained from experimental porphyria models -pharmacologically or genetically induced- are also described, which contributed to the classification of some drugs as prohibited for their use in porphyric patients. Finally, as porphyrins produce ROS and therefore cellular death, they can be used to treat infections by heme-deficient organisms like Trypanosoma cruzi and also as photosensitizers in photodynamic therapy (TFD).

Las porfirias son enfermedades metabólicas consecuencia de fallas en la biosíntesis del hemo, caracterizadas por un patrón específico de acumulación y excreción de intermediarios, responsables de su patofisiología. En las porfirias agudas el exceso de ácido d-aminolevúlico (ALA) produce una sintomatología neuroabdominal asociada al daño oxidativo por formación de especies reactivas de oxígeno (ROS), originadas por autooxidaxión del ALA. En las cutáneas, la sintomatología es producto de la acumulación de porfirinas, que como el ALA, inducen la formación de ROS. Su desencadenamiento se precipita por factores endógenos (ayuno, estrés, hormonas) y/o exógenos (fármacos), en particular algunos anestésicos. Se presenta una revisión de los estudios bioquímicos y genéticos en pacientes con diferentes porfirias obtenidos en el Centro de Investigaciones de Porfirias y Porfirinas (CIPYP), durante los últimos 38 años, que permitieron ampliar el conocimiento sobre las bases moleculares sobre estas patologías. Se describen los logros resultantes del empleo de modelos experimentales de porfiria, inducida farmacológica o genéticamente, que contribuyeron a la clasificación de algunas drogas como prohibidas para pacientes con porfiria. Finalmente, las porfirinas generadoras de ROS, y por ende inductoras de muerte celular, tienen su aplicación para combatir infecciones por organismos hemo-deficientes como Trypanosoma cruzi y también para ser utilizadas como fotosensibilizadores en la terapia fotodinámica (TFD).

Porphyrias are metabolism disorders caused by a partial deficiency in one of the heme biosynthetic pathway enzymes. Congenital Erythropoietic Porphyria, also termed Günther disease, is extremely rare and is inherited as an autosomal recessive trait that results from the markedly deficient activity of the fourth enzyme in the heme biosynthetic pathway, Uroporphyrinogen III synthase (UROIII-S). This enzyme deficiency leads to an increased production and accumulation of the nonphysiological and phototoxic type I porphyrins responsible for the typical clinical manifestations. The disease severity is markedly heterogeneous, ranging from severe transfusion dependency throughout life to milder adult cases with only cutaneous photosensitivity. Only 200 cases have been described all over the world so far. In this work five Argentinean CEP patients are presented, 4 infantile and one late onset case, diagnosed in the CIPYP which are, as far as it is known, the only cases described in Argentina. Increased amounts of porphyrins were found in plasma, blood, urine and faeces, together with high amounts of the pathogenic type I isomer. Enzyme activity was reduced to 25-44% respect to normal values. Early diagnosis is important for correct treatment so as to prevent the characteristic mutilation of the disease and to improve patient´s life quality.

Las porfirias son la consecuencia de fallas en el metabolismo del hemo. La Porfiria Congénita Eritropoyética (PCE) (enfermedad de Günther) es una porfiria cutánea rara que se transmite en forma autosómica recesiva. Se produce debido a la presencia de mutaciones en el gen de la uroporfirinógeno III sintetasa (UROIII-S) que llevan a una marcada disminución de su actividad y a la producción y acumulación de elevadas cantidades de porfirinas de la serie isomérica I en plasma, tejidos y huesos, responsables de la severa sintomatología cutánea que generalmente presentan los pacientes con esta porfiria. Se han descripto sólo alrededor de 200 casos a nivel mundial. Su expresión clínica es muy heterogénea, encontrándose desde casos muy graves con severo compromiso cutáneo, transfusión-dependiente, hasta casos leves con escasa sintomatología cutánea. Se presentan 5 casos de pacientes argentinos con PCE, 4 infantiles y uno de manifestación tardía, diagnosticados en el Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), que constituyen, hasta el momento, los únicos registrados en Argentina. Se encontraron elevadas cantidades de porfirinas en plasma, sangre, orina y materia fecal y un patrón de porfirinas con predominio de la serie I. La actividad de la UROIII-S estaba reducida en un 25-44% con respecto al valor normal. El diagnóstico certero y precoz de esta porfiria es fundamental para aplicar tempranamente el tratamiento adecuado en cada caso y brindarle al paciente una mejor calidad de vida.

Porphyrias are metabolic disorders caused by a decreased activity of one of the haem enzymes. Porphyria Cutanea Tarda (PCT) is due to subnormal activity of Uroporphyrinogen Decarboxylase (URO-D), and its value in erythrocytes allows differentiation between familiar and sporadic PCT, leading to increased levels of highly carboxylated porphyrins in liver, plasma and urine. Clinical symptoms include hyperpigmentation, hyperthricosis, blisters, skin photosensitivity and fragility. Factors such as alcohol, estrogens, polyhalogenated compounds, iron overload and infections with hepatitis viruses (HBV and HCV) and human immunodeficiency virus (HIV), have been implicated in its pathogenesis. All Argentine PCT-HIV cases studied from 1990 to 2004 were rewiewed. A group of 91 HIV positive subjects were diagnosed as PCT patients (20 to 50 years). Only 3 were women; 48 alcohol and drug abusers, 16 only heavy drinkers, 10 drug abusers and 41 were also coinfected with HCV. In 25 patients an overlapping of alcohol, drug abuse and HCV infection was found. In only 2 of the PCT-HIV studied URO-D was diminished. Treatment with low doses of chloroquine or the combined therapy (SAMe and chloroquine) is well tolerated, with normalization of clinical and biochemical signs. It can be concluded that HIV infected subjects should be considered a risk group, highly susceptible to developing Porphyria.

Las porfirias son consecuencia de una deficiencia parcial y específica de alguna de las enzimas del camino del hemo. En la Porfiria Cutánea Tardía (PCT) la deficiencia en la uroporfirinógeno decarboxilasa (URO-D) conduce a la acumulación de porfirinas altamente carboxiladas en hígado, plasma y orina. La enzima en sangre diferencia dos tipos de PCT: familiar y esporádica. Clínicamente presenta hiperpigmentación, hipertricosis, ampollas y fragilidad cutánea. En su patogénesis están implicados alcohol, estrógenos, drogas hepatotóxicas, compuestos polihalogenados, sobrecarga de hierro e infecciones con virus de hepatitis (VHC y VHB) y de la inmunodeficiencia humana (VIH). Se presenta una revisión de los pacientes PCT-VIH estudiados entre 1990 y 2004. Se diagnosticaron 91 individuos VIH como pacientes PCT (20 - 50 años), sólo 3 eran mujeres; 48 consumían alcohol y drogas de abuso, 16 consumían sólo alcohol, 10 eran adictos a drogas de abuso y 41 estaban coinfectados con VHC. En 25 pacientes había abuso de alcohol, drogas e infección con VHC. Sólo en 2 la URO-D estuvo disminuída. El tratamiento con bajas dosis de cloroquina y la terapia combinada (S-adenosil-L-metionina y cloroquina) fue bien tolerado con normalización de signos clínicos y bioquímicos. Se concluye que la población VIH positiva debería ser considerada como un grupo de riesgo de desarrollar PCT.

Em 1993 foi apresentado, no Congresso Brasileiro de Fruticultura, uma comunicação sobre anormalidades em tangerineiras 'Poncã', com suspeita de "greening", doença causada por bactérias não identificadas, devastadora da citricultura e ainda não assinalada no País. Os autores do presente trabalho visitaram o pomar com o problema no município de Perdões (MG) e notaram que praticamente todas as plantas do talhão apresentavam anomalias diversas. Os frutos mostravam-se normalmente pequenos, endurecidos, com sementes malformadas, casca espessa, o albedo com abundância de bolsas de goma, e caíam prematuramente. Nos ramos, havia morte da gema apical, poucas brotações novas, folhas onduladas com nervuras salientes e algumas com clorose no ápice do limbo. Por esses sintomas, suspeitou-se que a anomalia descrita fosse decorrente da carência de boro. Coletaram-se amostras de solo, de folhas e de frutos, e recomendou-se a aplicação foliar de boro. Essas análises revelaram carência moderada de zinco e severa de boro. A aplicação foliar desse nutriente proporcionou rápida recuperação das plantas. Exames elétrono-microscópicos em cortes ultrafinos de nervuras foliares e de columela de frutos afetados não revelaram indícios da presença de bactérias. Conclui-se, portanto, que a anomalia descrita é decorrente da carência de boro, em vez da incidência do "greening" dos citros, conforme descrito.

In 1993 abnormalities observed on Poncan mandarin (Citrus reticulata Blanco), in the area of Perdões, State of Minas Gerais, were suspected to be related to "greening", a citrus disease, not yet detected in Brazil. The affected plants presented very small and hard fruits, with thick and rough peel and drop prematurely. Cutting these fruits, conspicuous formation of gum pockets was seen in the albedo and some also in the flavedo, similar to boron deficiency. The seeds were dark and aborted. The normal fruits of the same trees did not show these symptoms. Leaf and fruit material were collected, as well as soil samples, at two depths. Leaves taken from symptomatic branches, have 6 to 12 tng/kg of boron, too low in relation with normal ones of 30 to 40 mg/kg. Leaf application of 1.5 mg/L of boric acid solution have promoted normal growth, 30 days after the application. Results of electronic microscopy did not indicate the presence of greening bacteria from neither foliar midribs nor fruits columella. A brief description of greening symptoms is presented. It was concluded that the abnormalities are due to boron deficiency instead of citrus greening as previously reported.