María García

Osteopenia in rats with liver cirrhosis: beneficial effects of IGF-I treatment.

BACKGROUND/AIMS Liver cirrhosis is associated with osteopenia and also with low levels of IGF-I. This hormone has been reported to stimulate bone formation in states of undernutrition and low bone turnover. Our aims were to evaluate whether osteopenia develops in male Wistar rats with CCl4-induced cirrhosis and whether IGF-I is effective in the restoration of bone mass in these animals. METHODS Cirrhotic rats were distributed into two groups: group CI (n = 12) which received placebo and group CI + IGF (n = 12) which was treated with human recombinant IGF-I (2 microg/100 g bw/day, s.c., 21 days). Twelve normal animals which received placebo constituted the control group. On the 22nd day, the animals were sacrificed, and bone parameters were analyzed in femur and/or tibia. RESULTS Posterior-anterior and latero-medial diameters were similar in all groups. Also, no significant differences were observed in bone contents of calcium, total proteins, collagen and hydroxyapatite in CI rats as compared with controls. However, CI rats showed significant reductions in bone weight (-13.5%, p < 0.001), total bone density (-9.28%, p < 0.001), and increased perimedullar bone resorption and urinary levels of deoxypyridinoline (a marker of bone resorption). In CI + IGF rats these parameters improved significantly as compared with CI animals. CONCLUSIONS Osteopenia characterized by loss of bone mass and preserved bone composition is found in rats with CCl4-induced cirrhosis. This bone disorder is partially corrected by treatment with low doses of IGF-I. Since osteoporosis seems to be the predominant form of osteopenia in patients with cirrhosis, IGF-I should be considered as a possible therapy for this disorder.

Antifibrogenic effect in vivo of low doses of insulin-like growth factor-I in cirrhotic rats.

Insulin-like growth factor-I (IGF-I) is produced mainly in the liver and it induces beneficial effects on the nutritional status, the liver function and oxidative hepatic damage in cirrhotic rats. The aim of this work was to analyze the effect of IGF-I on mechanisms of fibrogenesis in cirrhotic rats. Liver cirrhosis was induced by CCl(4) inhalation and phenobarbital in Wistar rats. Ten days after stopping CCl(4) administration (day 0), rats received either IGF-I (2 microg/100 g bw/day) (CI+IGF) or saline (CI) subcutaneously during 14 days. Animals were sacrificed on day 15. As control groups were used: healthy rats (CO) and healthy rats treated with IGF-I (CO+IGF). Liver histopathology, hydroxyproline content, prolyl hydroxylase activity, collagen I and III mRNA expression and the evolution of transformed Ito cells into myofibroblasts were assessed. Among the two control groups (CO+IGF), no differences were found in hydroxyproline content and these levels were lower than those found in the two cirrhotic groups. Compared with untreated cirrhotic rats, the CI+IGF-I animals showed a significant reduction in hydroxyproline content, prolyl hydroxylase activity and collagen alpha 1(I) and alpha1(III) mRNA expression. A higher number of transformed Ito cells (alpha-actin +) was observed in untreated cirrhotic animals as compared to CO and CI+IGF groups. In summary, treatment with IGF-I reduced all of the studied parameters of fibrogenesis. In conclusion, low doses of IGF-I induce in vivo an antifibrogenic effect in cirrhotic rats.

Effects of IGF-I treatment on osteopenia in rats with advanced liver cirrhosis.

IGF-I is an anabolic hormone which has been reported to increase bone formation in several conditions of undernutrition. Advanced liver cirrhosis is associated with osteopenia and also with low serum levels of IGF-I. Previous results showed that low doses of IGF-I increase osteoblastic activity and decrease bone reabsoption in early liver cirrhosis. The aim of this study was to evaluate whether IGF-I-treatment also induces beneficial effect on osteopenia associated with advanced cirrhosis. Rats with ascitic cirrhosis were divided into two groups: group CI (n=10) which received saline and group CI+IGF (n=10) which were treated with IGF-I (2 μg/100 g bw. day, sc, during 21 days). Healthy controls which received saline were studied in parallel (CO n=10). On the 22nd day, the animals were sacrificed, and bone parameters were analyzed in femur. Posterior-anterior diameter was similar in all groups. No significant differences were observed in bone content of calcium, total proteins, collagen and hydroxyapatite in cirrhotic rats as compared with controls. However, CI rats showed significant reductions in total bone density (−13.5%, p<0.001) assessed by densitometry) and radiological study. In CI+IGF rat bone density (assesed by densitometry) improved significantly as compared with CI animals. In summary, osteopenia characterized by loss of bone mass and preserved bone composition was found in rats with advanced cirrhosis induced by CCl4 and phenobarbital in drinking water. This bone disorder is partially restored by treatment with low doses of IGF-I during only three weeks. Thus, IGF-I could be considered as a possible therapy for osteopenia associated with advanced liver cirrhosis.ResumenIGF-I es una hormona anabólica con efecto sobre el metabolismo óseo. La cirrosis hepática avanzada está asociada con osteopenia y también con bajas concentraciones de IGF-I en suero. Resultados anteriores de nuestro grupo muestran que dosis bajas de IGF-I aumentan la actividad osteoblástica y reducen la resorción ósea en estadíos compensados de cirrosis hepática. El objetivo de este estudio consiste en evaluar si el tratamiento con IGF-I induce también un efecto beneficioso en la osteopenia asociada a cirrosis avanzada. Ratas con cirrosis ascítica se dividen en dos grupos: grupo CI (n=10), que reciben salino, y grupo CI+IGF (n=10) tratadas con IGF-I (2mg/100 g peso corporal/día, sc, durante 21 días). Controles sanos, que reciben salino, se estudian al mismo tiempo (CO n=10). El día 22, los animales se sacrifican y se analizan parámetros óseos en fémur. El diámetro antero-posterior es similar en todos los grupos. No se observan tampoco diferencias significativas en el contenido óseo (calcio, proteínas totales, colágeno, hidroxiapatita) en las ratas cirróticas al compararlas con los controles. Sin embargo, en los animales cirróticos se observa una reducción significativa de la densidad total ósea (−13.5%, p<0.001) medida por densitometría, reducción que se aprecia también en el estudio radiológico. En las ratas CI+IGF la densidad ósea mejora significativamente en comparación con los animales cirróticos sin tratamiento. En resumen, se observa osteopenia caracterizada por pérdida de masa ósea, en la que se preserva la normal composición del hueso, en ratas con cirrosis avanzada inducida por CCl4 y fenobarbital en el agua de bebida. Esta disminución de la masa ósea se recupera parcialmente por el tratamiento con dosis bajas de IGF-I durante sólo tres semanas. Por lo tanto, IGF-I podre ser considerado como una posible terapia para la osteopenia asociada a la cirrosis hepática en estadíos avanzados.

Local (gut) and systemic metabolism of rats is altered by consumption of raw bean (Phaseolus vulgaris L. var. athropurpurea )

The composition of the raw legume Phaseolus vulgaris L. var. athropurpurea (PhVa) and its effects on the metabolism of young growing rats have been evaluated. The levels of protein, unsaturated fatty acids, carbohydrate, fibre and bioactive factors present in PhVa were comparable with those in other Phaseolus vulgaris varieties. However, the lectins of PhVa were predominantly of the leucoagglutinating type, and concentrated in the albumin protein fraction. Rats fed a diet (110 g total protein, 16.0 MJ/kg) in which PhVa meal provided about half of the protein excreted high levels of N in faeces and urine, and grew more slowly, than rats fed a high-quality control diet (ad libitum or pair-fed). Small intestine, large intestine and pancreas weights were increased (by almost 100 %, P<0.05), whilst skeletal muscle, thymus and spleen weights were reduced. Blood insulin (16.20 v. 0.50 mU/l, P<0.05, thyroxine, glucose, protein (60.5 v. 48.3 g/l, P<0.05) and LDL-cholesterol were lowered, whilst glucagon (155.3 v. 185.4 ng/l, P<0.05), triiodothyronine and urea were elevated, as were urinary urea, creatinine and glucose. These changes in the local (gut) and systemic metabolism of rats were probably mediated primarily by lectins in PhVa, which were concentrated in the albumin protein fraction, whereas in many other Phaseolus vulgaris lines they are distributed across the globulin and albumin fractions.

IGF1 gene transfer into skeletal muscle using recombinant adeno-associated virus in a rat model of liver cirrhosis

Systemic administration of recombinant IGF1 at low levels has been shown to improve hepatic function, nutritional status and testicular atrophy in rats with CCl4-induced cirrhosis. We have developed a recombinant adeno-associated (rAAV) viral vector containing the cDNA for rat IGF1 and confirmed the expression of IGF1 after intramuscular injection of this vector in a rat model of liver cirrhosis. Although weight of injected muscles was significantly increased in rats with mild cirrhosis, this was not the case in rats with advanced, de-compensated cirrhosis. Furthermore, we found no significant amelioration of liver damage in treated rats at any stage of liver cirrhosis. Our results suggest that IGF1 gene transfer into muscle results in a local effect, at least at the vector dose employed here.ResumenLa administración sistémica de IGF1 a bajos niveles provoca mejoría de la función hepática, el estado nutricional y la atrofia testicular de las ratas con cirrosis hepática inducida por CCl4. En este trabajo, se ha desarrollado un vector viral adeno-asociado (rAAV) que contiene el cDNA de IGF1 de rata y se ha confirmado la expresión de IGF1 tras la inyección intramuscular de dicho vector en un modelo de cirrosis hepática en rata. Aunque el peso de los músculos tratados aumenta significativamente en ratas con cirrosis incipiente, este efecto no se reproduce en ratas con cirrosis avanzada y descompensada. Por otra parte, no se puede objetivar una mejoría del daño hepático en las ratas tratadas, independientemente del estado de la cirrosis que presentan. Nuestros resultados sugieren que la transferencia génica de IGF1 al músculo provoca un efecto local, al menos a las dosis de vector empleadas en este estudio.

IGF-I does not improve fat malabsorption in cirrhotic rats.

The aim of this study was to explore whether IGF-I treatment for two weeks modified fat intestinal absorption, measured from faecal content, in cirrothic and healthy rats. Male Wistar rats were used. Liver cirrhosis was induced by carbon tetrachloride (CCl4) inhalation twice a week for 11 weeks and phenobarbital addition to drinking water (400 mg/l) 1 week before an during the period of CCl4 exposure. Both control and cirrhotic rats were randomly assigned to two different groups to receive .the vehicle or IGF-I (2 mg/100mg bw day). The results show that faecal lipid content in cirrhotic animals significantly increases as compaired to control groups and no differences are found between untreated and IGF-treated cirrhotic animals. In summary, fat malabsorption observed in cirrothic animals is not corrected by the treatment with IGF-I

“The Discourse of the One Thousand Works”: The Seduction of History and Politics of Excess

In the 70s and 80s hot trading with architectural drawings started thanks to the role played by Schools and Institutions that, throughout publications and exhibitions, opened their treasures to the public. The postmodern cultural context for the celebration of the Centenary of the School of Architecture of Barcelona in 1977 was particularly specific in Spain due to the period of the political transition and the crisis of the architectural school. This paper will focus on how through an ideological use of drawing the reading of history in graphic terms could be used to propose a critical renovation of the architectural school rooted in what has constituted the discipline as so: the disciplinary drawing.