Improving the cadmium-induced centriacinar emphysema model in rats by concomitant anti-oxidant treatment.

1. The aim of the present study was to perform an evolutionary analysis of the morphometrical, biochemical and functional parameters of centriacinar emphysema induced by cadmium chloride (CdCl2) in rats and to determine the effects of concomitant N-acetylcysteine (NAC) administration. 2. Male Wistar rats were instilled orotracheally with either CdCl2 (n = 24) or saline (n = 24). One group of rats, consisting of both CdCl2- and saline-treated rats, was fed a normal diet (n = 24), whereas the other group received NAC (n = 24). 3. Changes in inspiratory capacity (IC), lung compliance (CL), expiratory flow at 75% (F75), forced vital capacity (FVC) and hydroxyproline content were assessed 2, 8, 21 and 45 days after instillation. Polymorphonuclear cells were evaluated 2 and 8 days after instillation and the mean linear intercept (Lm) was determined at 21 and 45 days. 4. Over time, CdCl2 instillation causes several changes that are bound up with centriacinar emphysema. The concomitant administration of NAC to CdCl2-treated rats partially reversed Lm at 21 days compared with CdCl2 alone (115 +/- 2 vs 127 +/- 2, respectively; P < 0.05). However, 45 days after instillation, NAC improved lung function in CdCl2-treated rats compared with that in the saline-treated control group (IC 14.64 vs 15.25, respectively (P = 0.054); FVC 16.94 vs 16.28, respectively (P = 0.052), F75 31.41 vs 32.48, respectively (P = 0.062)). In addition, 45 days after instillation, NAC reduced lung collagen content in both the saline-treated control (100 vs 81% alone and in the presence of NAC, respectively) and CdCL2-treated groups (213 vs 161% alone and in the presence of NAC, respectively). In addition, although the results were not significant, NAC tended to reduce Lm and enhance CL in NAC + CdCl2-treated rats. 5. In conclusion, NAC partially improved emphysematous changes and reduced collagen deposition, which diminished the CdCl2-induced fibrotic component of centriacinar emphysema.

Increased collagen deposition correlated with lung destruction in human emphysema.

BACKGROUND: To study the relationship between collagen amount and degree of emphysema as assessed by mean linear intercept (Lm) and correlating these with lung function test workup in patients with and without COPD. METHODS: Lung function tests were assessed in 16 smokers or ex-smokers and 1 non-smoker in order to separate them into two groups: COPD (FEV1/FVC lower than 70%) and non-COPD. A piece of lung tissue was used to analyse the collagen amount (HYP) by means of a colorimetric method. Morphometry was assessed to divide patients into two groups according to Lm: Lm > 260 micrometers was considered non-emphysema and Lm < 260 mm mild-emphysema. RESULTS: The non-emphysema group had a mean Lm value of 246.08+/-3.12 micrometers and the mild-emphysema group of 276.29+/-4.26 micrometers. The amount of hydroxyproline was significantly higher in the mild-emphysema group than in the non-emphysema group (7.82+/-0.67 vs. 5.50+/-0.54 microgram/g tissue). There was a clear positive correlation between Lm and HYP (r=0.55) and a negative correlation between Lm and DlCO (R=-0.5092). No correlation was found between the functional test and HYP, nor were there significant differences between COPD and non-COPD patients for Lm and HYP. CONCLUSIONS: Emphysema is associated with collagen deposition in the lungs, and air space size correlates with the amount of lung collagen even when there is no emphysema.

Naturally occurring neuronal death during postnatal development of the cerebellar nuclei in the rat / Muerte neuronal que ocurre de forma natural durante el desarrollo post-natal de los núcleos cerebelares de la rata

Naturally occurring neuronal death during the postnatal development of the cerebellar nuclei in the rat was analysed using classical cell counts and the labelling of fragmented DNA. Cell counts did not demonstrate a clear decrease in the number of cerebellar nuclei neurons along the first thirty days of postnatal life. However, the TUNEL technique revealed the existence of apoptotic cells with their DNA fragmented from the first to twentieth postnatal days. Apoptotic cells were randomly distributed throughout the cerebellar nuclei with no topographic preference and, in all cases, their numbers were very low, ranging from one to eight labelled cells per nucleus and section. The large amount of target (i.e., granule cells) that cerebellar nuclei neurons have could readily explain the absence of an important decrease in neuronal numbers during the postnatal development of these nuclei. The existence of apoptotic cells could be the expression of the withdrawal of neurons erroneously emplaced during the establishment of the refined topographic pattern of the cerebellar nucleo-cortical and cerebellofugal projections (AU)

Se analizó la muerte neuronal que ocurre de una manera natural durante el desarrollo post-natal de los núcleos cerebelosos de la rata utilizando conteos clásicos y el marcaje de DNA fragmentado. Los conteos no revelaron ningún descenso claro en el número de neuronas de los núcleos cerebelosos a lo largo de los primeros 30 días de vida post-natal. No obstante, la técnica TUNEL sí reveló la existencia de células apoptóticas cuyo DNA estaba fragmentado a partir del día 20 post-natal. Las células apoptóticas estaban distribuidas aleatoriamente por todos los núcleos cerebelosos, no mostrando ninguna preferencia topográfica, y en todos los casos sus números eran muy bajos, oscilando entre una y ocho células marcadas por núcleo y sección. La gran cantidad de diana (es decir, las células granulares) poseída por las neuronas de los núcleos cerebelosos fácilmente podría justificar la ausencia de un descenso importante en los números neuronales durante el desarrollo post-natal de estos núcleos. La existencia de células apoptóticas podría representar la expresión de la retirada de neuronas emplazadas de manera errónea durante el establecimiento del patrón topográfico refinado de las proyecciones cerebelosas núcleo-corticales y cerebelofugales (AU)