Partial splenic embolization and peg-IFN plus RBV in liver transplanted patients with hepatitis C recurrence: safety, efficacy and long-term outcome.

BACKGROUND: There is limited information on the long-term outcome in liver transplant (LT) subjects undergoing partial splenic embolization (PSE) prior to full dose pegylated interferon/ribavirin (peg-IFN/RBV). METHODS: Retrospective review of eight LT subjects after PSE and antiviral therapy. RESULTS: Baseline platelets and neutrophils were <50 000 cells/mL and <1000 cells/mL in 75% and 50%. Mean splenic infarction volume was 85 +/- 13%. PSE produced major complications in three (37.5%): recurrent sterile netrophilic ascites and renal insufficiency (n = 2), and splenic abscess (n = 1). Full-dose peg-IFN/RBV was started in seven (87.5%), with two early withdrawals (28.6%) despite early virological response (toxicity and infection); both subjects died. Anemia led to RBV dose-adjustment in six (86%), with human recombinant erythropoietin (EPO) use in four (57%). No peg-IFN adjustments or granulocyte-colonies stimulating factor were needed. Two patients reached sustained virological response (SVR) (28.6%). Two non-responders maintained prolonged therapy with biochemical/histological improvement. After a median follow-up of 151 wk, we observed significant improvements in hematological parameters, aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and prothrombin activity. CONCLUSIONS: Extensive PSE after LT produced significant morbidity (37.5%). Peg-IFN/RBV was completed in five out of seven (71%), with SVR in two (28.6%). RBV adjustement due to anemia was high despite EPO use. Only patients able to complete or maintain antiviral therapy survived, with long-term significant benefits in hematological parameters and liver function tests.

Variations in the cellular proliferation of prolactin cells from late pregnancy to lactation in rats.

Lactation is a physiological process associated with hyperactivity of hypophyseal prolactin-producing cells. It is known that the percentage of these cells is increased during lactation, although there are discrepancies in the reports regarding the mechanisms responsible for increasing the number of prolactin cells. In order to analyse whether this increase is a result of previous proliferation, variations in the proliferation rate of prolactin-positive cells were determined from late pregnancy to lactation in adult female rats by means of observation of the immunohistochemical expression of PCNA as a marker of cellular proliferation. During late pregnancy, a very significant increase in the percentage of proliferating prolactin cells was observed in comparison to non-pregnant females in the proestrus phase (p < 0.01). Although the percentage of prolactin-positive cells after one week of lactation was higher than in non-lactating or in pregnant females (p < 0.01), the proliferation rate was lower than in the other groups studied. In sum, our results suggest that late pregnancy constitutes a preliminary proliferative phase preparatory to the ensuing lactation phase and that endocrine changes in late pregnancy involve the cellular proliferation of hypophyseal prolactin cells in order to prepare the gland for later demands and to prevent proliferative changes from occurring during lactation.

Immunocytochemical evidence for growth hormone-releasing hormone in the tanycytes of the median eminence of the rat.

The current study was performed to analyse the potential existence and structure of a GHRH-transporting tuberoinfundibular system in the rat median eminence. The immunocytochemical analysis using anti-GHRH revealed an intense immunoreaction in the ependimary cells, tanycytes, at the level of the floor of the infundibular recess forming part of the median eminence. The basal processes of these cells course towards the external layer of the median eminence and reach the growth hormone-releasing hormone (GHRH) fibres of the tuberoinfundibular tract and this reaction was increased after intraventricular treatment with colchicine. Thus, these observations suggest the existence of a second or alternative cerebrospinal fluid-mediated route of GHRH transport to the median eminence and implicate the involvement of tanycytes in the regulation of this novel transport system.

The activity and proliferation of pituitary prolactin-positive cells and pituitary VIP-positive cells are regulated by interleukin 6.

Interleukins are proteins involved in the immune system and have been related to the endocrine regulation of the hypothalamic-pituitary-adrenal axis as well as to the secretion of ACTH, prolactin (PRL), GH and, possibly, LH. Like interleukin-6 (IL-6), vasoactive intestinal peptide (VIP) is synthesized in the pituitary gland and stimulates prolactin secretion. The aim of the present study was to address whether Interleukin 6 is involved in the regulation of VIP, as well as other factors involved in the regulation of prolactin such as dopamine, TRH and estradiol. Accordingly, we performed an in vitro study on monolayer cultures of rat pituitary cells, neutralizing the possible paracrine effect of IL-6 by immunosuppressing the protein by treatment with polyclonal antibody against IL-6 over 1, 3, 6 or 24 hours and then determining the degree of proliferation of VIP cells using double immunocytochemical labelling for VIP or PRL and proliferating cell nuclear antigen (PCNA). As a control, the effects of immunosuppression on the proliferation of PRL-positive cells were analyzed. Immunosuppression of IL-6 induced modifications in the cellular and nuclear size of VIP-positive cells, indicating an inhibitory process. Moreover, immunosuppression induced a significant decrease in the proliferation rate of PRL-positive or VIP-positive cells for all time-points analyzed. Similar effects on the proliferation rate of PRL-positive cells were found. The results of the present study demonstrate that IL-6 is involved in the regulation of the activity and proliferation of pituitary VIP-producing cells and suggest that, without ruling out a direct effect of IL-6 on prolactin cells, IL-6 could regulate prolactin by acting on pituitary VIP.