Chronic portal hypertension in the rat by triple-portal stenosing ligation.

A surgical technique based on the development of a triple stenosing ligation is used to worsen the complications inherent to the prehepatic chronic portal hypertension. The results have been compared with those obtained in rats with a single-portal stenosing ligation. An increase (p <.05) in the body, liver, spleen, and kidney weights as well as a decrease (p <.001) in the testes weight to body weight ratio were produced in both groups of animals. In addition, the variability in the obtained weights, particularly in the liver weight, stands out. The incidence of portosystemic and portohepatic collateral circulation and of the mesenteric venous vasculopathy increases in the animals with triple-portal stenosing ligation. The new proposed technique is a valid alternative to the classic one that used single portal stenosing ligation.

[Gene therapy in oncology: applications to lung cancer]. / Thérapie génique en oncologie: applications au cancer du poumon.

Gene therapy defines a new therapeutic avenue whose site of action is at the level of the gene itself; viral vectors (adenovirus, retrovirus, herpes virus) or non-viral (liposomes, plasmids) enable the transfer of a fraction of DNA (transgenic) to the target itself. In this review, we present recently acquired data on the mechanisms of oncogenesis and anti-tumor immunity which have enabled the application of several therapeutic strategies in oncology; the transfer of gene(s), coding for cytokines or for coactivation factors in order to develop active immunotherapy; the transfer of suicides genes; the transfer of multidrug resistance gene (MDR1); the transfer of tumor suppressor genes or of cDNA coding for antisense oligonucleotides in order to correct genomic anomalies which are responsible for the malign phenotype. The development of gene therapy demands the resolution of a number of technical difficulties such as vectorisation, targeting, and the expression of the stability of the trans-gene. Phase 1 trials in man have established the innocuity of certain vectors and have confirmed the expression of trans-genes (marker genes). Compared to monogenic hereditary diseases, the "molecular heterogenetic" of bronchial tumours, the consequence of the instability of the genome and the diversity of amplified oncogenes are a major difficulty. In addition, each one of these approaches prevents limiting factors: for example the exclusive targeting of malign cells is an indispensable pre-requisite for the transfer of suicide genes and in the same way the expression the tumour in antigens is the pre-requisite for the development of active immunotherapy. We report the overall results of applied trials for pulmonary carcinomas on murine models and present their applications which are underway in men.

Increased duodenal mucosa infiltration by mast cells in rats with portal hypertension.

BACKGROUND: Enteropathy characterized by vascular and inflammatory alterations in the submucosa and mucosa has been described in patients with portal hypertension. AIMS: To verify the theory of inflammatory etiopathogenesis in experimental portal hypertensive duodenopathy, a prehepatic portal hypertension model based on the development of a single and triple partial ligation of the portal vein was used in the rat. METHODS: Five rats in each group (male Wistar, 230-255 g) were subjected to single (group II) or triple (group III) partial ligation of the portal vein and then compared to 5 control animals (group I, no operation). The animals were sacrificed 6 weeks later to analyze the histological parameters of the duodenal mucosa and submucosa, i.e., number, diameter and area of submucosal vessels, density of mast cells and mitotic cells. Body, liver and spleen weights and collateral circulation type were also assayed. RESULTS: As was demonstrated by the collateral circulation in all of the animals, the partial portal ligation was successful. Compared to the controls, the number of vessels per microscopic field (25 +/- 3.16 vs. 18.60 +/- 1.52), their diameter (20.09 +/- 2.90 vs. 12.61 +/- 3.97 microm, p < 0.05) and consequently their total area (12,749.30 +/- 2,298.26 vs. 3,455.82 +/- 1,702.33 microm2) were increased in the animals with a single partial ligation (group II) as well as in animals receiving triple partial ligation (group III) (33 +/- 12.88, p < 0.05; 22.92 +/- 6.72 microm, p < 0.05 and 51,376.95 +/- 43,732.24 miccrom2, p < 0.05, respectively). In addition, the density of mast cells increased from 3.26 +/- 1.18 in controls to 10.74 +/- 1.47, p < 0.01 and 22.50 +/- 6.42, p < 0.01 in single and triple partial portal ligated animals, respectively. Mitosis was significantly induced in crypts of the duodenal mucosa of the single portal ligated animals (25.20 +/- 1.78 vs. 17.40 +/- 1.14, p < 0.01) but was inhibited in triple partial ligated animals (12.40 +/- 5.12, p < 0.05). Compared to controls, both groups of rats developed liver atrophy with a greater decrease in the liver/body weight ratio in the single (2.71 +/- 0.50%, p < 0.01) compared to the triple partial ligated animals (3.33 +/- 0.09%, p < 0.01). CONCLUSIONS: The correlation of the degree of portal hypertension with the vascular changes and mast cell density suggests that both the hypertensive state and inflammation may play a role in the development of portal hypertensive intestinal vasculopathy. The inverse relation of portal hypertension with liver atrophy and mitosis rate in the crypts of the duodenal mucosa has not been clarified and should be investigated in future studies.