Brief topical and intraluminal use of Carolina rinse solution does not attenuate experimental ischemia and reperfusion injury in rabbit jejunum / [O uso tópico breve e intraluminal da solução de Carolina rinse não atenua a injúria de isquemia e reperfusão experimental no jejuno de coelhos ]

Fifteen New Zealand adult rabbits were randomly allocated into three groups: Sham-operated (group A), Ischemia and Reperfusion (group B) and Carolina Rinse Solution (CRS) (group C). Groups B and C were subjected to one hour of ischemia and two hours of reperfusion. In group C, ten minutes before reperfusion, the bowel lumen was filled with CRS, and the segment immersed in CRS. Necrosis and loss of integrity of the villi were visible in groups B and C. Edema of the submucosa and circular muscle was observed in all groups. Hemorrhage was observed in different layers for groups B and C, but group C showed more severe hemorrhage in different layers during reperfusion. All groups showed polymorphonuclear leukocyte infiltration on the base of the mucosa, submucosa, and longitudinal muscle, in addition to polymorphonuclear leukocytes margination in the mucosal and submucosal vessels. Necrosis of enterocytes, muscles, crypts of Lieberkühn and myenteric plexus was observed in groups B and C during reperfusion. Topical and intraluminal Carolina Rinse Solution did not attenuate the effects of ischemia and reperfusion in the small intestine of rabbits.(AU)

Quinze coelhos da raça Nova Zelândia foram alocados em três grupos: instrumentado (grupo A), isquemia e reperfusão (grupo B) e solução de Carolina rinse (CRS) (grupo C). Os grupos B e C foram submetidos a uma hora de isquemia e a duas horas de reperfusão. No grupo C, 10 minutos antes da reperfusão, o segmento isolado foi imerso e teve seu lúmen preenchido com CRS. Os grupos B e C apresentaram necrose e perda progressiva da integridade das vilosidades. Foi observado edema na submucosa e na camada muscular circular em todos os grupos. Nos grupos B e C, foi observada hemorragia em diferentes camadas, mas, no grupo C, a hemorragia foi mais intensa durante a reperfusão. Todos os grupos apresentaram infiltrado de PMN na base da mucosa, na submucosa e na camada muscular longitudinal e marginação de PMN nos vasos da mucosa e da submucosa. Durante a reperfusão, foi observada necrose dos enterócitos, das camadas musculares, das criptas de Lieberkühn e do plexo mioentérico nos grupos B e C. O uso tópico e intraluminal de CRS não atenuou os efeitos da isquemia e da reperfusão no intestino delgado de coelhos.(AU)

Deferoxamine Improves Alveolar and Pulmonary Vascular Development by Upregulating Hypoxia-inducible Factor-1alpha in a Rat Model of Bronchopulmonary Dysplasia

Fetal lung development normally occurs in a hypoxic environment. Hypoxia-inducible factor (HIF)-1alpha is robustly induced under hypoxia and transactivates many genes that are essential for fetal development. Most preterm infants are prematurely exposed to hyperoxia, which can halt hypoxia-driven lung maturation. We were to investigate whether the HIF-1alpha inducer, deferoxamine (DFX) can improve alveolarization in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was produced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85% for 7 days), and DFX (150 mg/kg/d) or vehicle was administered to rat pups intraperitoneally for 14 days. On day 14, the rat pups were sacrificed and their lungs were removed and examined. A parallel in vitro study was performed with a human small airway epithelial cell line to test whether DFX induces the expression of HIF-1alpha and its target genes. Alveolarization and pulmonary vascular development were impaired in rats with BPD. However, DFX significantly ameliorated these effects. Immunohistochemical analysis showed that HIF-1alpha was significantly upregulated in the lungs of BPD rats treated with DFX. DFX was also found to induce HIF-1alpha in human small airway epithelial cells and to promote the expression of HIF-1alpha target genes. Our data suggest that DFX induces and activates HIF-1alpha, thereby improving alveolarization and vascular distribution in the lungs of rats with BPD.

Evaluación de efectividad y seguridad de deferasirox en Hemosiderosis Transfusional / Evaluation of effectiveness and safety of deferasirox in Hemosiderosis Transfusional

Antecedentes: Descripción de la condición de salud de interés (indicación): El cuerpo humano no posee un mecanismo activo para la excreción de hierro, y sus niveles son controlados principalmente por su absorción en el intestino delgado. Fisiológicamente, la cantidad de hierro absorbido (1-2mg/dia) se pierde mediante exudados de la mucosa intestinal y piel, así como pequeñas cantidades a través de la orina y bilis. Los pacientes que cursan con anemias crónicas y que son dependientes de transfusiones sanguíneas, reciben un exceso de hierro con cada transfusión (cada unidad de glóbulos rojos contiene aproximadamente 250mg de hierro); este hierro es acumulado de forma gradual en diferentes tejidos, tales como corazón e hígado. Descripción de la tecnología: El deferasirox es un medicamento quelante, trifdentado que se une especialmente al hierro; es empleado en el tratamiento de la sobrecarga crónica de este metal en el organismo. Está disponible en comprimidos para administración por vía oral. Cuenta con registro sanitario en Colombia. Evaluación de efectividad y seguridad: En pacientes con diagnóstico de hemosiderosis transfusional ¿cuál es la efectividad y seguridad de deferasirox comparado con deferoxamina, en la reducción de depósitos de hierro hepático o cardíaco, niveles de ferritina sérica y mortalidad? La pregunta de investigación fue validada teniendo en cuenta las siguientes fuentes de información: registro sanitario INVIMA, Acuerdo 029 de 2011, guías de práctica clínica, revisiones sistemáticas y narrativas de la literatura, estudios de prevalencia/incidencia y carga de enfermedad, libros de texto, consulta con expertos temáticos, sociedades científicas y otros actores clave. Población: pacientes con diagnóstico de hemosiderosis transfusional. Tecnología de interés: Deferasirox. Conclusiones: Efectividad: Deferasirox es una alternativa terapéutica de administración oral, efectiva para el tratamiento de la hemosiderosis transfusional. No existen diferencias significativas en mortalidad entre deferasirox y deferoxamina. La efectividad de deferasirox puede ser similar a deferoxamina dependiendo de la dosis y proporción comparada; sin embargo, la satisfacción de los pacientes es mayor en el grupo de pacientes previamente tratados con deferoxamina, que recibieron posteriormente deferasirox, lo que puede llevar a una mejor adherencia al tratamiento. Seguridad: los eventos adversos más frecuentes se encuentran relacionados con síntomas gastrointestinales, sin diferencias estadísticamente significativas entre ambos agentes. Sin embargo, se demuestra una mayor probabilidad de presentar aumento en los niveles de creatinina sérica con deferasirox en comparación con deferoxamina.

[Hearing status of thalassemic patients treated with deferoxamine]

Major beta thalassemia is the most common inherited anemia with high prevalence in Iran and hearing loss is one of its side effects. The present study aimed to determine the hearing status of patients with major thalassemia and its relationship with serum ferritin level, period of blood transfusion and deferoxamine administration. This descriptive-analytic study was performed on 80 thalassemia major patients [36 Male and 44 Female] aged 4-32 [14.2 +/- 2.3] who were referred to Bou Ali Hospital for two years. The studied variables include age, gender, serum ferritin level, amount and duration of Desferal injection and hearing level. All subjects went under evaluation for their otologic and audiometric status. The collected data were analyzed using t-test and ANOVA with SPSS software. The findings of the study indicated that 38 patients [47%] had entirely hearing loss. Among these 38 patients, 17 patients had sensory neural type f hearing loss 12 patients had conductive and 7 patients had mixed type of hearing problems. The results showed a significant relationship [p<0.05] between hearing loss and serum ferritin level and the dosage and duration of Desferal administration. Hearing impairment may develop with increasing dosage of deferoxamine. Periodic follow up and physical examination is recommended to prevent hearing impairment in major thalassemia

High-dose deferoxamine treatment [intravenous] for thalassaemia patients with cardiac complications

As a means to manage cardiac conditions, we determined the effects of high-dose intravenous [IV] deferoxamine in 15 thalassaemia patients with cardiomyopathy and high ferritin and haemoglobin levels. The patients received IV deferoxamine, 130 mg/kg per day over 10-14 hours [maximum 5 g] for 5 consecutive days. All patients underwent a full evaluation before receiving deferoxamine, and 2 days and 1 month after completing the treatment. Visual and auditory examinations were done to detect any side-effects. After treatment, cardiovascular symptoms decreased considerably and systolic function showed significant improvement, but there was no significant effect on diastolic function, electro-cardiography and physical findings. There were no significant side-effects reported

Autoantibodies in thalassaemia major: relationship with oral iron chelator L1.

Ninety patients with thalassaemia major were investigated for the occurrence of antinuclear antibodies (ANA), and those with ANA were tested for antibodies to histones (AHA). ANA were detected in 7 of 27 thalassemics on oral iron chelator L1, and in 2 of 63 thalassaemics not on L1 (p < 0.01). AHA were seen in 4 of 7 thalassemics receiving L1 with positive ANA, and in none of the 2 not receiving L1 (p < 0.03). Joint pains were seen in patients receiving L1, but in none of the patients not receiving L1. There was no correlation between hepatitis B or HIV positivity and presence of ANA or joint pains. While some amount of background ANA-positivity was found in patients with thalassaemia major, it was significantly more in patients receiving L1. Laboratory evidence of drug-induced lupus-like reaction was seen only in patients who received L1. In view of serious concerns about the safety of L1 and wide variations in the incidence and severity of adverse reactions reported by different sources, an urgent regulatory audit of all trial centres is essential.

Anemia falciforme: cuidados pré, per e pós-operatórios / Sickle cell anemia: pre, per and postoperatory care

Os autores abordam os aspectos fisiopatológicos e os cuidados pré, per e pós-operatórios de pacientes portadores de drepanocitose. Propöem, através de um quadro padronizado, as condutas e cuidados relativos a pacientes cirúrgicos portadores desta doença. Apresentam, ainda uma paciente com drepanocitose, com incterícia obstrutiva por cálculo no colédoco distal, submetida à cirurgia, na qual foi aplicada padronizaçäo proposta, com boa evoluçäo no pós-operatório

A desferoxamina e seu efeito protetor na preservaçäo pulmonar / Diferoxamin and its protective effect in pulmonary preservation

Há recentes evidências de que radicais livres derivados do oxigênio estao envolvidos na lesao tecidual decorrente de isquemia e subseqüente reperfusao. A desferoxamina (DF), evitando a produçao de radicais hidroxila e eliminando o ânion superóxido, pode atenuar este dano, sendo seus efeitos aqui avaliados após quatro horas de preservaçao pulmonar hipotérmica. O auto-transplante pulmonar esquerdo foi realizado em 12 caes mestiços. O pulmao foi, inicialmente, perfurado com 1000 ml de soluçao de Collins modificada e mantido insuflado, colocado sob refrigeraçao (4 graus Celsius) em soluçao salina durante quatro horas. Seis caes receberam 500 mg de DF administrados E.V. durante o período isquêmico e imediatamente após iniciar a reperfusao. Após reimplante e ligadura da artéria pulmonar direita, os animais foram mantidos numa FiO(2) fixa (49 por cento) e monitorizados por quatro horas. Durante a primeira hora pós-reperfusao, o pO(2) arterial foi sifnificativamente superior no grupo tratado com DF (p < O.05). O gradiente alvéolo-arterial foi também inferior (p < O.05). A resistência vascular pulmonar foi semelhante em ambos os grupos. Concluímos que a desferoxamina permite melhor troca gasosa no período imediatamente após reperfusao e que sua investigaçao, na área da preservaçao pulmonar, deve ser estimulada.

Iron excretion in thalassemia children treated with deferoxamin methansulfonat: intravenous drip compared to the subcutaneous routes.

The iron excretion in the three beta-Thal/Hb E patients were determined comparing the effect of DF given by subcutaneous push, subcutaneous drip and intravenous drip. The subcutaneous drip or intravenous drip increased urine iron excretion by 5.6-11.2 times whereas the subcutaneous push, 3.5-5.3 times only. It is recommended that for countries where the infusion machine is very expensive the DF should be given by intravenous drip or the modified, simple and inexpensive equipment for subcutaneous drip.

Síndrome de 5q- anemia refractaria, trombocitosis e hipolobulación de megacariocitos / 5q- syndrome: refractory anemia, thrombocytosis and hypolubulation of megakaryocytes

Se describe el caso de una mujer de raza blanca, de 30 años de edad, con anemia crónica de 3 años de evolución, refractaria a tratamiento médico y a esplenectomía. Los estudios citogenéticos demostraron una anomalía única, la delección parcial del brazo largo del cromosoma No. 5, defecto denominado "Síndrome del 5q-" descrito en aproximadamente 15 pacientes en la literatura mundial. Este síndrome aparentemente adquirido se caracteriza por anemia refractaria, moderada leucopenia, trombosistosis e hipolobulación de los megacariocitos. La anemia es resistente a los tratamientos conocidos y no evoluciona a leucemia aguda. La mayor parte de los pacientes fallecen por las complicaciones de la hemosiderosis producida por la gran cantidad de transfusiones que requieren para mantener una hemoglobina adecuada. La terapia quelante de hierro con desferroxamina, utilizando minibombas de infusión continua, es, hasta el momento, la única forma de prevenir la muerte por falla cardíaca en los pacientes dependientes de transfusiones. Este es el primer caso del "Síndrome del 5q-" informado en la literatura médica colombiana